Systems and methods for multifunctional volumetric fluid control

ABSTRACT

Systems and methods for controlling fluid movement and volumes of fluid between a subject and a controlled compliant flow path. The controlled compliant flow path has a means for selectively metering in and metering out fluid from the controlled compliant flow path. An extracorporeal flow path is in fluid communication with the controlled compliant flow path across a semi-permeable membrane where the extracorporeal flow path has a first terminal end and a second terminal end.

FIELD OF THE INVENTION

This disclosure relates to systems and methods for controlling fluidmovement and volumes of fluid between a subject and a controlledcompliant flow path. The systems and methods can be used in a medicaltherapy device for delivering any one of hemodialysis, hemodiafiltrationand hemofiltration for the treatment of pathological conditions such asEnd Stage Renal Disease (ESRD). The systems and methods are configurablewith a modular system having a dialyzer, control components, dialysateregeneration cartridge and fluid reservoirs capable of operating free ofa high volume of purified water source and drain utilities andinfrastructure. A separate supply of packaged or prepared sterile salineis not required for priming, fluid bolus, or blood rinse back when usingthe present invention. The systems and methods are configured to be usedin medical therapy devices and systems that have a suitable weight anddesign to be optionally transportable by an individual including by thepatient. The systems and methods are simple and intuitive to operate andmaintain. Moreover, the systems and methods are sufficiently compactsuch that little space is required for the device during storage ortransport.

BACKGROUND

Chronic Kidney Disease (CKD), also known as chronic renal disease, maybe a sudden or progressive loss in renal function. As the diseaseseverity progresses, a patient with severe renal failure develops manysymptoms that, if left untreated, eventually result in death. The mostsevere stage of CKD is End Stage Renal Disease (ESRD). ESRD, alsoreferred to as kidney failure or renal failure, is the medical conditionwherein a person's kidneys fail to sufficiently remove toxins, wasteproducts, and excess fluid, and to maintain proper electrolyte levels.

Current treatments for CKD seek to manage comorbidities and, ifpossible, slow the progression of the disease. However, as the diseaseprogresses, renal function decreases and eventually renal replacementtherapy is employed to compensate for lost kidney function. Renalreplacement therapy typically entails transplantation of a new kidney,or dialysis. Kidney dialysis is a medical procedure that is performed toaid or replace some of the kidney functions in severe renal failure.Hemodialysis, hemofiltration, hemodiafiltration, and peritoneal dialysisare all replacement therapies for patients who have lost most or all oftheir kidney function. Dialysis can remove many of the toxins and wastesthat the natural kidney would remove. In addition, these therapies areused to balance the electrolyte or blood salt levels and to removeexcess fluid that accumulates in patients with renal failure.

Hemodialysis treatment can be performed to remove waste products fromthe blood that are no longer being effectively removed by the kidneys,such as urea, creatinine and phosphates. Although the population ofpatients afflicted with CKD grows each year, there is no cure. Theexcess fluid accumulated in patients suffering from renal failure isgenerally removed by the ultrafiltration action of a dialysis procedure.

Hemodialysis procedures in developed countries are usually carried outthree times a week in three to five hour sessions. In some geographies,hemodialysis is less available and conducted less frequently. Dialysisemulates kidney function by removing waste solutes, excess electrolytesand excess fluid from a patient's blood. During dialysis, the patient'sblood that contains a high concentration of waste solutes is exposed toa semi-permeable membrane in contact with a solute-deficient dialysissolution (dialysate). Solute removal and electrolyte balancing isaccomplished via diffusion across the membrane. Fluid removal isaccomplished via pressure-driven convective transport through themembrane, commonly referred to as ultrafiltration. Once the blood ispurified, it is then returned to the patient. Although effective atremoving wastes from blood, dialysis treatments are administeredintermittently and therefore do not emulate the continuous function of anatural kidney. Moreover, there are many inconveniences associated withdialysis, such as the necessity of traveling to a dialysis center andcommitting to time consuming treatments multiple times per week.

Although hemodialysis removes excess fluid, interdialytic intervals of ahemodialysis schedule create variations in the patient's waste removal,impurity removal, fluid removal and electrolyte balance. Thesevariations result in patient complications and the high rates of patientmorbidity and mortality. Since the mid-1990s a number of physicians haveprescribed treatment regimens with increased dialysis frequency andtreatment time to try to eliminate the problems associated with thethrice-weekly hemodialysis schedule. Two recent randomized controlledclinical studies have shown statistically significant benefits of a morefrequent dialysis regimen. Culleton et al. (Culleton, B F et al. Effectof Frequent Nocturnal Hemodialysis vs. Conventional Hemodialysis on LeftVentricular Mass and Quality of Life. 2007 Journal of the AmericanMedical Association 298 (11)) reported that when compared withconventional hemodialysis (trice weekly) daily nocturnal hemodialysisimproved left ventricular mass (a surrogate for mortality), reduced theneed for blood pressure medications and improved some measures ofmineral metabolism. The FHN trial (The FHN Trial Group. In-CenterHemodialysis Six Times per Week versus Three Times per Week, New EnglandJournal of Medicine, 2010) was a comparison of increased treatmentfrequency of 5.2 hemodialysis treatments a week compared with thetraditional thrice-weekly regimen: “Frequent hemodialysis, as comparedwith conventional hemodialysis, was associated with favorable resultswith respect to the composite outcomes of death or change in leftventricular mass and death or change in a physical-health compositescore.” Based on this data it would be desirable to have a hemodialysissystem that would allow kidney patients to dialyze from five to sevendays a week, if not continuously.

Despite the clinical results from the Culleton and FHN research, fewpatients presently undergo a higher frequency of dialysis treatment.More frequent hemodialysis is only used on a small part of the patientpopulation due to the burden and cost of more frequent therapies. Eventhe thrice weekly-regime is a significant burden to ESRD patients, andan increase in treatment frequency can often be difficult due to thedeficiencies in known devices and the cost of the additional treatments.Most dialysis is performed in a dialysis center; hence, there is a needfor the practical implementation of more frequent hemodialysis using asimple, wearable/portable, and safe technology that can be used by apatient at home.

Typical home-dialysis equipment employs an amount of dialysis fluidgreater than 20 liters, up to 120 liters or more, that must be producedby a dedicated water purification system. The typical requirement forlarge amounts of purified water creates a barrier in that stationary,expensive, and often architecturally incompatible water purificationsupply and drain systems must be connected to the plumbing.

A different water-related barrier to treatment exists in some developingregions of the world, in that infrastructure to produce the largevolumes of purified water may not exist within feasible travelingdistance for persons suffering from ESRD. Thus, a dialysis therapysystem that does not require large volumes of purified water couldincrease availability of life-saving hemodialysis therapy for thosesuffering from ESRD in such regions. In such regions, a system that canprovide dialysis therapy from just a few liters of potable or bottleddrinking water is of special value. In developing regions, or even indeveloped regions suffering from natural disaster, a model fordelivering life-saving hemodialysis therapy can be mobile dialysis unitsthat can travel to the location where therapy is needed and provide theneeded therapy. Equipment that is compact, lightweight, and free ofrequirements for large volumes of purified water, and not requiring ahigh ratio of skilled technicians per patient to operate the equipmentis the equipment of choice for this therapy delivery modality.

The large volume of dialysate fluid required for dialysis is in partattributable to the large quantity of solution necessary for thediffusion of waste products removed and the balancing of electrolyteswithin the dialysate from the blood of a dialysis patient. Regenerationof spent dialysate is one way to reduce the total volume of a dialysissystem by eliminating the need for a large reserve of fresh dialysate.However, existing technologies for regenerating spent dialysate havebeen met with various limitations. For example, the RecirculatingDialysate System (“REDY system”) may be subject to variations in pH andsodium concentrations that depart from physiological norms.Additionally, REDY systems have limited or no ability to removesulfates, and may not be easily portable by the individual receivingtherapy.

Development of dialysate recirculating techniques has resulted insystems that employ a variety of sorbent media, including activatedcarbon, urease, and zirconium-, aluminum-, and magnesium-basedmaterials. Yet one of the problems associated with sorbent regenerationof spent dialysate is the buildup of sodium ions released as a byproductof the adsorption process, thus necessitating a high degree of sodiumconcentration control which has yet to be achieved by currentlyavailable wearable or portable dialysis systems.

Some systems have attempted to address the volume and weight problems byallowing for external connections to a tap water source. However, theintroduction of tap water into a dialysis system necessitates additionalpurification measures, thus adding to system complexity and size. As aresult, such systems may not be useful for mobile or portable use.

Sorbent-based dialysate regeneration systems can be found in U.S. Pat.No. 3,669,878 Marantz et al., which describes sorbent removal of ureaand ammonium ions from spent dialysate via urease, ammonium carbonate,and zirconium phosphate; U.S. Pat. No. 3,669,880 Marantz et al., whichdescribes directing a controlled volume of dialysate through zirconiumphosphate, activated carbon, and hydrated zirconium oxide columns; U.S.Pat. No. 3,850,835 Marantz et al., which describes production of azirconium hydrous oxide ion exchange media; and U.S. Pat. No. 3,989,622Marantz et al., which describes adsorption of urease on aluminum oxideand magnesium silicate media to convert liquid urea to ammoniumcarbonate.

U.S. Pat. No. 4,581,141 Ash describes removal of uremic substances fromdialysate via a calcium-based cation exchanger, urease, and aliphaticcarboxylic acid resin. U.S. Pat. No. 4,826,663 Alberti et al. describesa method of preparing a zirconium phosphate ion exchanger. U.S. Pat. No.6,627,164 Wong describes production of sodium zirconium carbonate forion exchange in renal dialysis, and U.S. Pat. No. 7,566,432 Wongdescribes production of zirconium phosphate particles for ion exchangein regenerative dialysis. U.S. Pat. No. 6,818,196 Wong, U.S. Pat. No.7,736,507 Wong, U.S. Application Publication 2002/0112609 Wong, U.S.Application Publication 2010/0078387 Wong, and U.S. ApplicationPublication 2010/00784330 Wong, describe cartridges for purification ofdialysis solutions using sodium zirconium carbonate.

U.S. Pat. No. 6,878,283 Thompson, U.S. Pat. No. 7,776,210 Rosenbaum etal., U.S. Application Publication 2010/0326911 Rosenbaum et al., U.S.Application Publication 2010/0078381 Merchant, U.S. ApplicationPublication 2009/0127193 Updyke et al. and U.S. Application Publication2011/0017665 Updyke et al. describe filter cartridges having a pluralityof types of filter media including zirconium compounds, urease, andalumina for dialysis systems. WO 2009/157877 A1 describes a ureasematerial having urease immobilized on a substrate intermixed with acation exchange material or zirconium phosphate material to improveworkability for the reduction of clogging and to improve absorption ofammonium ions generated by the urease.

Management of impurities in regenerated dialysate can be found in U.S.Pat. No. 4,460,555 Thompson and U.S. Pat. No. 4,650,587 Polak et al.,which describes magnesium phosphate media for removal of ammonia fromaqueous solutions, U.S. Application Publication 2009/0282980 Gura etal.; “A Study on the Temperature Variation of Rise Velocity for LargeClean Bubbles,” Leifer et al., J. Atmospheric & Oceanic Tech., Vol. 17,pp 1392-1402; “Terminal Velocity of a Bubble Rise in a Liquid Column,”Talaia, World Acad. of Sci., Engineering & Tech., Vol. 28, pp. 264-68;U.S. patent application Ser. No. 12/937,928 to Beck; U.S. Pat. No.5,468,388 to Goddard et al.; U.S. patent application Ser. No. 12/182,489to Kirsch; U.S. patent application Ser. No. 12/355,128 to Gura et al.;U.S. Pat. No. 4,371,385 to Johnson; U.S. Pat. No. 4,381,999 to Boucheret al.; U.S. patent application Ser. No. 12/516,786 to Wallenborg etal.; U.S. Pat. No. 4,828,693 to Lindsay et al.; U.S. Pat. No. 5,762,782to Kenley et al.; U.S. Pat. No. 7,981,082 to Wang et al.; and U.S.patent application Ser. No. 13/100,847 to Palmer.

There is a need for systems and/or methods that can simplify andautomate these tasks for those individuals suffering from ESRD who areunable to access a dialysis centers, or who prefer not to. There is alsoa further need for expansion of hemodialysis therapy to individuals, orthose living in developing regions where there is limited spaceavailable for the equipment at the home including those individualssuffering from ESRD who live in a single room shared by multipleindividuals.

In particular, there is a need to provide a system that can produceultrapure solution from potable water or other types of water suitablefor dialysis that does not require sterile saline to perform thesefunctions.

SUMMARY OF THE INVENTION

The present invention describes a system for controlling fluid movementbetween a subject and a controlled compliant flow path. In anyembodiment, the system can have a controlled compliant flow path havinga means for selectively metering in and metering out fluid from thecontrolled compliant flow path; and an extracorporeal flow path in fluidcommunication with the controlled compliant flow path across asemi-permeable membrane. In any embodiment, the extracorporeal flow pathcan have a first terminal end and a second terminal end.

In any embodiment, the system for controlling fluid movement can have afirst terminal end and the second terminal end connectable together toform a junction.

In any embodiment, the system for controlling fluid movement can have ajunction between the terminal ends of an arterial line and a venous lineof an extracorporeal circuit.

In any embodiment, the system for controlling fluid movement can have anextracorporeal flow path with a blood pump for circulating blood throughthe extracorporeal flow path, and a first valve and/or a second valve toselectively permit flow through a first conduit and a second conduit influid communication across either a dialyzer or hemofilter on theextracorporeal flow path.

In any embodiment, the system for controlling fluid movement can have ameans for selectively metering in and metering out fluid from thecontrolled compliant flow path with a control pump in fluidcommunication with a control reservoir.

In any embodiment, the system for controlling fluid movement can have acontrol pump coordinately operating with a first valve and/or a secondvalve to control fluid movement.

In any embodiment, the system for controlling fluid movement can have atleast the blood pump coordinately operating with the first and/or secondvalve to control fluid movement.

In any embodiment, the system for controlling fluid movement can havethe control pump and a blood pump on the extracorporeal flow pathcoordinately operating with the first valve and/or second valve tocontrol fluid movement.

In any embodiment, the system for controlling fluid movement can havethe extracorporeal flow path having a hydrophobic vent or a primingoverflow reservoir connected to the junction.

In any embodiment, the system for controlling fluid movement can have atleast one of the first valve or second valve being a pinch valve.

In any embodiment, the system for controlling fluid movement can have asorbent cartridge on the controlled compliant flow path. In anyembodiment, a fluid can pass through the sorbent cartridge prior tocrossing the semi-permeable membrane.

In any embodiment, the system for controlling fluid movement can have amicrobial filter on the controlled compliant flow path. In anyembodiment, a fluid can pass through the microbial filter prior tocrossing the semi-permeable membrane.

In any embodiment, the system for controlling fluid movement can have amicrobial filter on the controlled compliant flow path. In anyembodiment, fluid can pass through the microbial filter prior toentering the extracorporeal flow path.

In any embodiment, the system for controlling fluid movement can have atleast one bubble detector to detect air in the extracorporeal flow pathat any one of a first conduit, a second conduit, or both.

In any embodiment, the system for controlling fluid movement can havethe controlled compliant flow path with a means for conductivitymeasurement to verify that a sodium content is within predeterminedlimits.

In any embodiment, the system for controlling fluid movement can havethe controlled compliant flow path with a means for adjusting the soluteconcentration of fluid in the controlled compliant flow path.

In any embodiment, the system for controlling fluid movement can have ameans for adjusting the solute concentration of fluid in the controlledcompliant flow path. In any embodiment, a sodium chloride source canincrease a sodium chloride concentration of fluid passing through thecontrolled compliant flow path and a buffer source can increase a bufferconcentration of fluid passing through the controlled compliant flowpath.

In any embodiment, the system for controlling fluid movement can have ameans for adjusting the solute concentration of fluid in the controlledcompliant flow path. In any embodiment, a sodium chloride cartridge canincrease a sodium chloride concentration of fluid passing through thecartridge and a buffer source cartridge can increase a bufferconcentration of fluid passing through the buffer source cartridge.

The present invention also describes a reservoir for use in a system forperforming any one of hemodialysis, hemodiafiltration, hemofiltration.In any embodiment, the reservoir can have a control pump in fluidcommunication with a controlled compliant flow path; and a commonreservoir in fluid communication with a control pump. In any embodiment,the common reservoir can contain any one of a dialysate, a filtrate, avolume of a physiologically compatible priming solution, a volume of aphysiologically compatible solution to provide a bolus of fluid to asubject receiving treatment, a volume of physiologically compatiblesolution to provide solution for return of blood from an extracorporealflow path to a subject receiving treatment, a volume of solutionreturned to the common reservoir from an extracorporeal flow path whenblood from a subject is introduced to the extracorporeal flow path, andcombinations thereof.

In any embodiment, the reservoir can have the dialysate produced by thesystem for performing hemodialysis or hemodiafiltration from waterintroduced to a conduit of a controlled compliant flow path, a sorbentcartridge, a source of sodium introduced to a conduit of the controlledcompliant flow path, and optionally solutes other than sodium introducedto a conduit of the controlled compliant flow path.

In any embodiment, the reservoir can have the volume of aphysiologically compatible priming fluid produced by the system fromwater introduced to a conduit of a controlled compliant flow path, asorbent cartridge, a source of sodium introduced to a conduit of thecontrolled compliant flow path, and optionally solutes other than sodiumintroduced to a conduit of the controlled compliant flow path.

In any embodiment, the reservoir can have the volume of aphysiologically compatible solution provide a bolus of fluid to asubject receiving treatment produced by the system from water introducedto a conduit of the controlled compliant flow path, a sorbent cartridgeand a source of sodium introduced to a conduit of the controlledcompliant flow path, and optionally solutes other than sodium introducedto a conduit of the controlled compliant flow path.

In any embodiment, the reservoir can have the volume of aphysiologically compatible solution provide fluid volume for return ofblood from the extracorporeal flow path to a subject receiving treatmentproduced by the system from water introduced to a conduit of thecontrolled compliant flow path, a sorbent cartridge, and a source ofsodium introduced to a conduit of the controlled compliant flow path,and optionally solutes other than sodium introduced to a conduit of thecontrolled compliant flow path.

In any embodiment, the reservoir can have a portion of the fluid volumecontained in the reservoir originating from a spent dialysate, afiltrate from the blood of a subject, or a priming fluid that has beenreturned to the controlled compliant flow path from the extracorporealflow path.

In any embodiment, the reservoir can have the physiologically compatiblepriming fluid delivered from the common reservoir to a conduit of thecontrolled compliant flow path in fluid communication with anextracorporeal flow path for priming of the extracorporeal flow path. Inany embodiment, the priming fluid can be passed through a sorbentcartridge and at least a microbial filter or a dialyzer membrane.

In any embodiment, the reservoir can have a volume of fluid returned tothe common reservoir from an extracorporeal flow path when blood from asubject is introduced to the extracorporeal flow path.

In any embodiment, the reservoir can have the volume of physiologicallycompatible solution to provide solution for return of blood from anextracorporeal flow path to a subject receiving treatment passed througha sorbent cartridge and optionally infused by a source of cationsintroduced to a conduit of the controlled compliant flow path to producethe dialysate or a replacement fluid.

In any embodiment, the reservoir can have the volume of aphysiologically compatible solution to provide a bolus of fluid to asubject receiving treatment first passed through a sorbent cartridge andat least a microbial filter or dialyzer membrane prior to being returnedto the extracorporeal flow path.

In any embodiment, the reservoir can have the volume of aphysiologically compatible priming solution, the volume of aphysiologically compatible solution to provide a bolus of fluid to asubject receiving treatment, the volume of physiologically compatiblesolution to provide solution for return of blood from an extracorporealflow path to a subject receiving treatment, the volume of solutionreturned to the common reservoir from an extracorporeal flow path whenblood from a subject is introduced to the extracorporeal flow path, andcombinations thereof drained from the common reservoir followingconclusion of a treatment.

In any embodiment, the reservoir can have the volume of fluid in thereservoir further comprising fluids that are drained from theextracorporeal flow path, the controlled compliant flow path, or aninfusate reservoir following conclusion of a treatment.

In any embodiment, the system for controlling fluid movement can be usedin a method of priming a dialyzer and extracorporeal flow path. In anyembodiment, this method can include operating a control pump to transfera first volume of fluid from the control reservoir to a controlledcompliant flow path; opening a second valve on the extracorporeal flowpath while operating the control pump to transfer a second volume offluid from the control reservoir to the controlled compliant flow path;closing the second valve; opening an first valve on the extracorporealflow path while coordinately operating the control pump and blood pumpto transfer a third volume of fluid from the control reservoir to thecontrolled compliant flow path and to the extracorporeal circuit;closing the first valve and stopping the control pump and the blood pump

In any embodiment, the method of priming a dialyzer and extracorporealflow path using the system for controlling fluid movement can have thefirst volume of fluid being approximately equal to the priming volume ofa dialyzer or a hemofilter. In any embodiment, opening the second valvecan cause an equal volume of fluid to move to the extracorporeal flowpath, the second volume being approximately equal to the priming volumeof the second conduit of the extracorporeal flow path; and the thirdvolume being approximately equal to the priming volume of the firstconduit.

In any embodiment, the method of priming a dialyzer and extracorporealflow path using the system for controlling fluid movement can includeoperating a circulating pump to move air from the dialyzer to adegassing module in fluid communication with the controlled compliantflow path.

In any embodiment, the method of priming a dialyzer and extracorporealflow path using the system for controlling fluid movement can includeopening the first and second valves and operating the blood pump tocirculate the priming fluid through the extracorporeal circuit; closingthe first valve and stopping the blood pump; operating the control pumpto transfer a fourth volume of priming fluid to the controlled compliantflow path to cause an equal volume of fluid to move through the secondconduit to a priming overflow reservoir in fluid communication with thejunction; closing the second conduit and operating the control pump totransfer a fifth volume of fluid from the control reservoir to thecontrolled compliant flow path while operating the blood pump incoordination with the control pump to cause an equal volume of fluid tomove through a first conduit to a priming overflow reservoir in fluidcommunication with the junction.

In any embodiment, the system for controlling fluid movement between asubject and a controlled compliant flow path can include a method ofreturning a priming fluid and initiating a therapy session. In anyembodiment, this method can include connecting the first terminal end toa first blood access connection of a subject; opening a first valve onthe extracorporeal flow path while operating a blood pump; stopping theblood pump and closing the second valve and disconnecting the secondterminal end from the overflow reservoir, and connecting the secondterminal end to a second blood access connection of a subject.

In any embodiment, the method of returning a priming fluid andinitiating a therapy session can include opening the first valve to movea predetermined volume of blood into the extracorporeal flow path anddisplace an approximately equal volume of priming fluid to an overflowreservoir in fluid communication with the second terminal end.

In any embodiment, the method of returning a priming fluid andinitiating a therapy session using the system for controlling fluidmovement between a subject and a controlled compliant flow path caninclude connecting the second terminal end to a first blood accessconnection of the subject; opening a second valve on the extracorporealflow path while operating a control pump to move a predetermined firstvolume of blood into the extracorporeal flow path; stopping the controlpump and closing the second valve and connecting the first terminal endto a second blood access connection of the subject; opening a firstvalve and operating a blood pump and the control pump together atapproximately equal volumetric flow rates to move a second volume ofblood into the extracorporeal flow path.

In any embodiment, the method of returning a priming fluid andinitiating a therapy session using the system for controlling fluidmovement between a subject and a controlled compliant flow path caninclude displacing an approximately equal volume of priming fluid from afirst segment of the extracorporeal flow path across the semipermeablemembrane to a control reservoir on the controlled compliant flow path;and displacing an approximately equal volume of priming fluid from asecond segment of the extracorporeal flow path across the semipermeablemembrane to the control reservoir. In any embodiment, the first andsecond predetermined volumes can be approximately equal to the totalpriming volume of the extracorporeal flow path.

In any embodiment, a method of returning a priming fluid and initiatinga therapy session using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can includeconnecting the first terminal end to a first blood access connection ofthe subject; opening a first valve on the extracorporeal flow path whileoperating a control pump to move a predetermined first volume of bloodinto the extracorporeal flow path; stopping the control pump and closingthe first valve and connecting the second terminal end to a second bloodaccess connection of the subject; opening a second valve and operating ablood pump and the control pump together at approximately equalvolumetric flow rates to move a second volume of blood into theextracorporeal flow path.

In any embodiment, a method of returning a priming fluid and initiatinga therapy session using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can includedisplacing an approximately equal volume of priming fluid from a firstsegment of the extracorporeal flow path across the semipermeablemembrane to a control reservoir on the controlled compliant flow path;and displacing an approximately equal volume of priming fluid from asecond segment of the extracorporeal flow path across the semipermeablemembrane to the control reservoir. In any embodiment, the first andsecond predetermined volumes can be approximately equal to the totalpriming volume of the extracorporeal flow path.

In any embodiment, the method of returning a priming fluid andinitiating a therapy session using the system for controlling fluidmovement between a subject and a controlled compliant flow path caninclude either the blood or control pump being a bidirectional pump.

In any embodiment, a method for delivering a fluid bolus to a subjectusing the system for controlling fluid movement between a subject and acontrolled compliant flow path can include transferring a predeterminedvolume of the physiological-compatible fluid from the control reservoirto the controlled compliant flow path to cause thephysiological-compatible fluid to transverse a dialyzer membrane or amicrobial filter from the controlled compliant flow path to theextracorporeal flow path; and conveying the physiologically compatiblefluid through the extracorporeal conduit flow path to the subject.

In any embodiment, a method for delivering a fluid bolus to a subjectusing the system for controlling fluid movement between a subject and acontrolled compliant flow path can have the predetermined volume of thephysiological-compatible fluid from the control reservoir being equal tothe volume of the physiological-compatible fluid. In any embodiment, thevolume of the physiologically compatible fluid can be equal to thevolume in the extracorporeal conduit flow path.

In any embodiment, a method for delivering a fluid bolus to a subjectusing the system for controlling fluid movement between a subject and acontrolled compliant flow path can include measuring the conductivity ofthe fluid before it passes to the extracorporeal flow path.

In any embodiment, a method for delivering a fluid bolus to a subjectusing the system for controlling fluid movement between a subject and acontrolled compliant flow path can include operating an infusate pump toadjust a concentration of a solute in the fluid before the fluid passesto the extracorporeal flow path.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can includetransferring a volume of fluid from the control reservoir to thecontrolled compliant flow path to cause a volume of the fluid totransverse a dialyzer membrane or a microbial filter from the controlledcompliant flow path to the extracorporeal flow path; and conveying thevolume of the physiologically compatible fluid through theextracorporeal flow path to the subject.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can include thevolume of fluid from the control reservoir to the controlled compliantflow path causing an equal volume of the fluid to transverse a dialyzermembrane or a microbial filter from the controlled compliant flow pathto the extracorporeal flow path. In any embodiment, the volume of thephysiologically compatible fluid can be equal to the volume conveyedthrough the extracorporeal flow path to the subject.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have theequal volume being approximately equal to a priming volume of theextracorporeal flow path.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can includeconveying a first volume of the fluid through a first segment of theextracorporeal flow path; and conveying a second volume of the fluidthrough a second segment of the extracorporeal flow path. In anyembodiment, transferring the first volume of the fluid from the controlreservoir to the controlled compliant flow path can cause a first equalvolume of the fluid to transverse the semipermeable membrane from thecontrolled compliant flow path to the extracorporeal flow path, andtransferring the second volume of the fluid from the control reservoirto the controlled compliant flow path can cause a second equal volume ofthe fluid to transverse the semipermeable membrane from the controlledcompliant flow path to the extracorporeal flow path.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have thefirst volume of the fluid approximately being equal to a first primingvolume of the first segment of the extracorporeal flow path and thesecond volume of the fluid approximately being equal to a second primingvolume of the second segment of the extracorporeal flow path.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have a bloodpump and a control pump operated coordinately to convey fluid through aconduit of the extracorporeal flow path.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have thecontrol pump being a bidirectional pump.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have theextracorporeal flow path having a blood pump for circulating bloodthrough the extracorporeal flow path, and a first valve and/or a secondvalve to selectively permit flow through the tubing forming theextracorporeal flow path.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have themeans for selectively metering in and metering out fluid from thecontrolled compliant flow path being a control pump in fluidcommunication with a control reservoir.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have at leastthe control pump coordinately operating with a first valve and/or asecond valve to control fluid movement.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have at leastthe blood pump coordinately operating with the first valve and/or secondvalve to control fluid movement.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have thecontrol pump and a blood pump on the extracorporeal flow pathcoordinately operating with the first valve and/or second valve tocontrol fluid movement.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can have at leastone of the first valve or second valve being a pinch valve.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can include thestep of passing a fluid through a sorbent cartridge on the controlledcompliant flow path. In any embodiment, the fluid can pass through thesorbent cartridge prior to crossing the semi-permeable membrane into theextracorporeal flow path.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can include thestep of passing a fluid though a microbial filter on the controlledcompliant flow path. In any embodiment, the fluid can pass through themicrobial filter prior to crossing the semi-permeable membrane into theextracorporeal flow path.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can include thecontrolled compliant flow path has a means for conductivity measurementto verify that a sodium content is within predetermined limits.

In any embodiment, a method for returning blood from an extracorporealflow path to a subject using the system for controlling fluid movementbetween a subject and a controlled compliant flow path can include thecontrolled compliant flow path having a means for adjusting theconductivity of fluid in the controlled compliant flow path.

SUMMARY OF THE DRAWINGS

FIG. 1 shows a hemodialysis device having a controlled compliant flowpath and jumpered ports in accordance with certain embodiments.

FIG. 1A shows components of a controlled compliant flow path that may bedisposable or consumable, together with jumpered ports in accordancewith certain embodiments.

FIG. 1B shows a base module portion of a controlled compliant flow pathand jumpered ports of a hemodialysis device having a range of positionswhere the salination inflow can be drawn from the main controlledcompliant flow path.

FIG. 1C shows the active portion of a fluid circuit for a hemodialysisdevice having a controlled compliant flow path during de-aeration ofwater contained in a water supply reservoir.

FIG. 1D shows a hemofiltration device having a controlled compliancefiltrate regeneration circuit and jumpered ports in accordance withcertain embodiments.

FIG. 1E shows a hemodiafiltration device having a controlled compliancedialysate and replacement fluid circuit and jumpered ports in accordancewith certain embodiments.

FIG. 2 shows a hemodialysis device having a controlled compliant flowpath comprising a user interface, a controller, a base module, a therapycassette, a sorbent cartridge, and a water reservoir.

FIG. 3 shows a hemodialysis device having a controlled compliant flowpath and jumpered ports in a configuration for cleaning and/ordisinfection of the controlled compliant flow path in accordance withcertain embodiments.

FIG. 4A shows the patient blood access connector ends of theextracorporeal flow path joined at a tee connection with fluid overflowreservoir for storage of excess priming fluid in accordance with certainembodiments.

FIG. 4B shows the patient blood access connector ends of theextracorporeal flow path joined at a hydrophobic vent for release of airduring priming in accordance with certain embodiments.

FIG. 4C shows the patient blood access connector ends of theextracorporeal flow path connected to separate inlet and outlet ports ofan overflow reservoir for priming of an extracorporeal flow path inaccordance with certain embodiments.

FIG. 5A shows a hemodialysis device in configuration for storage ortransport stowage in accordance with certain embodiments.

FIG. 5B shows hemodialysis device in transport configuration inaccordance with certain embodiments.

FIG. 5C shows a user interface and shelf doors deployed on the main bodyof a hemodialysis device base module in “set-up ready” configurationwith fluid connection ports exposed in accordance with certainembodiments.

FIG. 5D shows an example of an integrated therapy disposables andconsumables cassette, sorbent cartridge, and water supply reservoirinstalled on a hemodialysis device with a cassette latching mechanism inaccordance with certain embodiments.

FIG. 5E shows an example of a therapy disposables and consumablescassette, sorbent cartridge, and connected water supply reservoir inaccordance with certain embodiments.

FIG. 5F shows an example of a therapy solution reservoir (controlreservoir) deployed on a hemodialysis device in accordance with certainembodiments.

FIG. 5G shows a front and back side of an arrangement of disposables andconsumables into an integrated therapy cassette with fluid connectionports in accordance with certain embodiments.

FIG. 6A shows a front and back side of a cleaning manifold with anintegrated flush fluid reservoir, fluid circuit jumpers, control valves,and fluid connection ports for use with the hemodialysis device inaccordance with certain embodiments.

FIG. 6B shows a water reservoir, a cleaning and disinfection manifold,and a cartridge containing cleaning and/or disinfection agent installedon a hemodialysis device in accordance with certain embodiments.

FIG. 6C shows a hemodialysis device folded into storage and stowedtransport configuration yet having a cleaning manifold remain in placein accordance with certain embodiments.

FIG. 7A shows a mating fluid connection port configuration for fluidcommunication between a fluid pathway of a base module and a fluidpathway of a therapy cassette.

FIG. 7B shows a mating fluid connection port configuration for fluidcommunication between a cleaning and disinfection manifold and a fluidpathway of a base module.

FIG. 8 shows a method of operating a hemodialysis device in accordancewith certain embodiments.

FIG. 9 shows a method of setting up a hemodialysis device in accordancewith certain embodiments.

FIG. 10 shows a method of setting up a hemodialysis device in accordancewith certain embodiments.

FIG. 11 shows a method of priming a hemodialysis device in certainembodiments.

FIG. 12 shows a method of performing therapy using a hemodialysis devicein certain embodiments.

FIG. 13 shows a method of rinsing blood back using a hemodialysis devicein accordance with certain embodiments.

FIG. 14 shows a method of evacuating a hemodialysis device in accordancewith certain embodiments.

FIG. 15 shows a method of cleaning and disinfecting a hemodialysisdevice in certain embodiments.

FIG. 16 shows a schematic of a degassing module in certain embodiments.

FIG. 17 shows another schematic of a degassing module in certainembodiments having fluid inlet and outlet ports at different elevations.

FIG. 18 shows an isometric view of the exterior of a degassing module.

FIG. 19 shows a fluid flow through a bicarbonate cartridge in accordancewith certain embodiments.

FIG. 20 shows two views of a bicarbonate cartridge in certainembodiments.

Throughout the figures and the specification, components with the samenumbers in the FIG.'s refer to the same components.

DETAILED DESCRIPTION OF THE INVENTION Definitions

Unless defined otherwise, all technical and scientific terms used hereingenerally have the same meaning as commonly understood by one ofordinary skill in the relevant art. The definitions provided hereinshould not be rigidly construed without taking into account the contextand other ascribed meanings provided, or by their use, in other parts ofthe specification, claims, and drawings.

The articles “a” and “an” are used herein to refer to one or to morethan one (i.e., to at least one) of the grammatical object of thearticle. By way of example, “an element” means one element or more thanone element.

An “acid” can be either an Arrhenius acid, a Brønsted-Lowry acid, or aLewis acid. The Arrhenius acids are substances or fluids which increasethe concentration of hydronium ions (H3O+) in solution. TheBrønsted-Lowry acid is a substance which can act as a proton donor.Lewis acids are electron-pair acceptors

The term “cation infusate pump” historically known as an “acidconcentrate pump” in dialysis systems refers to a pump that serves thefunction to move or control the flow of a fluid to and/or from areservoir having a substance that contains at least one cation species,such as calcium, magnesium and potassium ions. In the present invention,the historically used term of “acid concentrate pump” is used.

The term “activated carbon” refers to a porous carbon material having asurface area greater than 500 m² per gram. Activated carbon can becapable of absorbing several species including heavy metals such aslead, mercury, arsenic, cadmium, chromium and thallium among others,oxidants such as chlorine and chloramines, fluoride ions, and wastespecies such as phosphate and certain nitrogen-containing waste speciessuch as creatinine and uric acid.

The terms “administering,” “administer,” “delivering,” and “deliver,”can be used in context to indicate the provision of water; aqueoussolutions such as saline and dialysate that may contain salts acids,bases, and sugars; anticoagulant; or therapeutics such as erythropoietinand vitamins to a dialysate, dialysis circuit, or extracorporeal flowpath where such water, or agent will enter the blood of the patient bydiffusion, transversal of a diffusion membrane or other means.

The term “air trap” refers to a structure for separating a gas from amixture of a gas and a liquid or any other separation means known in theart. An air trap can include a hydrophobic membrane for allowing gasesto pass and for preventing the passage of water.

The term “albumin sieving coefficient” can be used to describe theamount of albumin that will cross a membrane.

The terms “ammonia sensing module” and “ammonia detector” refer to aunit that performs all or part of the function to detect a predeterminedlevel of, or measure a concentration of, ammonia and/or ammonium ions ina fluid.

The term “anticoagulant” is a substance that prevents or delays theclotting of blood, such as heparin, Fragmin®, and sodium citrate.

The term “atmospheric pressure” refers to the local pressure of air inthe environment in proximity to the system at the time that the systemis operating.

A “base” can be either a substance that can accept hydrogen cations(protons) or more generally, donate a pair of valence electrons. Asoluble base is referred to as an alkali if it contains and releaseshydroxide ions (OH—) quantitatively. The Brønsted-Lowry theory definesbases as proton (hydrogen ion) acceptors, while the more general Lewistheory defines bases as electron pair donors, allowing other Lewis acidsthan protons to be included.[1] The Arrhenius bases act as hydroxideanions, which is strictly applicable only to alkali.

The term “base module” refers to a basic unit of an apparatus forhemodialysis, hemodiafiltration, or hemofiltration that incorporates oneor more fluid pathways. Exemplary, non-limiting components that can beincluded in the base module include conduits, valves, pumps, fluidconnection ports, sensing devices, a controller and a user interface.The base module can be configured to interface with reusable ordisposable modules of the apparatus for hemodialysis, hemodiafiltration,or hemofiltration to form at least one complete fluid circuit, such as adialysis, cleaning, disinfection, priming or blood rinse back circuit.

The term “bicarbonate buffer component” refers to any compositioncontain bicarbonate (HCO3-) ion or a conjugate acid of bicarbonate ionin any amount, proportion or pH of the composition. The bicarbonatebuffering system is an important buffer system in the acid-basehomeostasis of living things, including humans. As a buffer, it tends tomaintain a relatively constant plasma pH and counteract any force thatwould alter it. In this system, carbon dioxide (CO2) combines with waterto form carbonic acid (H2CO3), which in turn rapidly dissociates to formhydrogen ions and bicarbonate (HCO3-) as shown in the reactions below.The carbon dioxide-carbonic acid equilibrium is catalyzed by the enzymecarbonic anhydrase; the carbonic acid-bicarbonate equilibrium is simpleproton dissociation/association and needs no catalyst.CO₂+H₂O⇄H₂CO₃⇄HCO₃ ⁻+H⁺

Any disturbance of the system will be compensated by a shift in thechemical equilibrium according to Le Chatelier's principle. For example,if one attempted to acidify the blood by dumping in an excess ofhydrogen ions (acidemia), some of those hydrogen ions will associatewith bicarbonate, forming carbonic acid, resulting in a smaller netincrease of acidity than otherwise.

The term “bicarbonate cartridge” refers to a container that can be astand-alone container or alternatively can be integrally formed with anapparatus for hemodialysis, hemodiafiltration, or hemofiltration. Thebicarbonate cartridge can store a source of buffering material, such assodium bicarbonate, and can be configured to interface with at least oneother functional module found in systems for hemodialysis,hemodiafiltration, or hemofiltration. For example, the bicarbonatecartridge can contain at least one fluid pathway and include componentssuch as conduits, valves, filters or fluid connection ports. Thebicarbonate cartridge can be disposable or be consumable wherein thecartridge is recharged upon depletion. Specifically, the term“bicarbonate consumables container” refers to an object or apparatushaving or holding a material in solid and/or solution form that is asource of bicarbonate, such as sodium bicarbonate, that is depletedduring operation of the system. The object or apparatus may be singleuse, or may be replenished and used multiple times, for example, byrefilling the object to replace the consumed material.

The term “bidirectional pump” refers to a device configured to performwork on a fluid to cause the fluid to flow alternatively in either oftwo opposing directions.

A “biocompatible material” is a material that has the ability tointerface with living biological tissues with an acceptable hostresponse in any of specific medical systems, methods of treatment ordelivery contemplated herein. The biocompatible material can consist ofsynthetic, natural or modified natural polymers intended to contact orinteract with the biological systems during application of any of theinventions contained herein.

The term “blood access connection” refers to a junction or aperturethrough which the blood of a subject is conveyed to or from anextracorporeal circuit. Commonly, the blood access connection is madebetween a terminal end of a conduit of an extracorporeal circuit and theterminal end of a catheter or fistula needle that is distal to thesubject receiving therapy. A subject may have more than one blood accessconnection when receiving therapy. In the case of two blood accessconnections they can be referred to as an arterial blood accessconnection and a venous blood access connection.

The term “blood rinse back” refers to returning the blood from adialyzer and/or extracorporeal circuit to a subject, normally atconclusion of a therapy session and prior to disconnecting or removingthe subject's blood access connection or connections. The procedure caninclude conveying a physiologically compatible solution through theextracorporeal circuit to push or flush the blood from theextracorporeal circuit to the subject via the subject's blood accessconnection or connections.

The term “bolus” refers to an increase (or at times a decrease) oflimited duration in an amount or concentration of one or more solutes,for example sodium, glucose and potassium, or a solvent, for examplewater, such that the concentration of a solution is changed. The term“bolus” includes delivery of solute and/or solvent to the dialysatefluid path such that it is delivered to the blood of a subject viadiffusion and/or convection across a dialysis membrane such that theamount or concentration in the subject is increased or decreased. A“bolus” may also be delivered directly to the extracorporeal flow pathor the blood of a subject without first passing through the dialysismembrane.

The term “bottled water” refers to water that may be filtered orpurified and has been packaged in a container. Bottled water can includewater that has been packaged and provided to a consumer as drinkingwater.

The terms “bubble detector”, “bubble sensor”, “gas detector” and “airdetector” refer to a device that can detect the presence of a void, voidspace, or gas bubble in a liquid.

The term “buffer source” refers to a stored material, such asbicarbonate, acetate or lactate that provides buffering.

The term “buffer conduit flow path” refers to a fluid flow path in fluidcommunication with a stored source of a buffering material, such asbicarbonate.

The term “buffer source” refers to a stored material, such asbicarbonate, acetate or lactate that provides buffering.

The terms “buffer source container” and “buffer source cartridge” referto objects that have or hold one or more materials, in solid and/orsolution form, that are a source of buffering, for example abicarbonate, a lactate, or acetate; and the object further having atleast one port or opening to allow at least a portion of the bufferingmaterial to be released from the object during operation of the system.

The terms “bypass circuit,” “bypass conduit,” “bypass flow path,”“bypass conduit flow path” and “bypass” refer to a component orcollection of components configured or operable to create an alternatefluid pathway to convey a fluid around one or more other components of afluid circuit such that at least a portion of the fluid does not contactor pass through the one or more other components. At times the term“shunt” may be used interchangeable with the term “bypass” When any ofthe above “bypass” terms listed in this paragraph are used in context asbeing part of a controlled compliant system, then the relevantreferenced “bypass” has the proper characteristics as to operate withina controlled compliant system as defined herein

The term “cartridge” refers to a compartment or collection ofcompartments that contains at least one material used for operation ofthe system of the present invention.

The term “cassette” refers to a grouping of components that are arrangedtogether for attachment to, or use with the device, apparatus, orsystem. One or more components in a cassette can be any combination ofsingle use, disposable, consumable, replaceable, or durable items ormaterials.

The term “cation infusate source” refers to a source from which cationscan be obtained. Examples of cations include, but are not limited to,calcium, magnesium and potassium. The source can be a solutioncontaining cations or a dry composition that is hydrated by the system.The cation infusate source is not limited to cations and may optionallyinclude other substances to be infused into a dialysate or replacementfluid, non-limiting examples can be glucose, dextrose, acetic acid andcitric acid.

The term “cation concentrate reservoir” refers to an object having orholding a substance that is comprised of at least one cation, forexample calcium, magnesium, or potassium ions.

“Chronic kidney disease” (CKD) is a condition characterized by the slowloss of kidney function over time. The most common causes of CKD arehigh blood pressure, diabetes, heart disease, and diseases that causeinflammation in the kidneys. CKD can also be caused by infections orurinary blockages. If CKD progresses, it can lead to end-stage renaldisease (ESRD), where the kidneys fail to function at a sufficientlevel.

The term “citric acid” refers to an organic acid having the chemicalformula C₆H₈O₇, and may include anhydrous and hydrous forms of themolecule, and aqueous solutions containing the molecule.

The term “cleaning and/or disinfection concentrate” refers to a drysubstance or solutions containing at least one material for use incleaning and/or disinfection of an apparatus.

The term “cleaning and/or disinfection solution” refers to a fluid thatis used for the purpose of removing, destroying or impairing at least aportion of at least one contaminant. The contaminant may be organic,inorganic or an organism. The fluid may accomplish the purpose bytransmission of thermal energy, by chemical means, flow friction or anycombination thereof.

The terms “cleaning manifold” and “cleaning and disinfection manifold”refer to an apparatus that has fluid connection ports and one or morefluid pathways, or fluid port jumpers, that, when connected to jumperedports of a base module, create a one or more pathways for fluid to beconveyed between the jumpered ports of the base module. A cleaningmanifold may be further comprised of additional elements, for examplevalves and reservoirs.

The term “common container,” “common cartridge,” or “common reservoir,”and the like refer to an object or apparatus that can hold more than onematerial; however, the time of holding more than one material may or maynot necessarily be at the same time. The material(s) may be in solidand/or solution forms and may be held in separate compartments withinthe object or apparatus.

The term “common fluid inlet port” refers to an opening or aperturethrough which all fluid first passes to enter an object, apparatus orassembly.

The term “common fluid outlet port” refers to an opening or aperturethrough which all fluid passes to exit an object, apparatus or assembly.

The terms “communicate” and “communication” include, but are not limitedto, the connection of system electrical elements, either directly orremotely, for data transmission among and between said elements. Theterms also include, but are not limited, to the connection of systemfluid elements enabling fluid interface among and between said elements.

The terms “component” and “components” refer to a part or element of alarger set or system. As used herein, a component may be an individualelement, or it may itself be a grouping of components that areconfigured as a set, for example, as a cassette or a cleaning and/ordisinfection manifold.

The term “comprising” includes, but is not limited to, whatever followsthe word “comprising.” Thus, use of the term indicates that the listedelements are required or mandatory but that other elements are optionaland may or may not be present.

The term “concentrate pump” refers to a device that can perform work ona fluid solution to cause the fluid to flow and can actively control thetransfer of fluid volume such as an infusate or an acid concentrate intoa circuit.

The terms “conditioning conduit flow path” or “conditioning flow path”refer to a fluid pathway, circuit or flow loop that incorporates asource of a conditioning material, for example a sodium salt orbicarbonate.

The term “conditioning flow path inlet” refers to a location on aconditioning flow path where fluid enters the conditioning flow path.

The term “conditioning flow path outlet” refers to a location on aconditioning flow path where fluid exits the conditioning flow path.

The term “conductive species” refers to a material's ability to conductan electric current. Electrolytes are an example of a conductive speciesin dialysate fluids, such as, but not limited to the presence sodium,potassium, magnesium, phosphate, and chloride ions. A fluid's ability toconduct an electrical current is due in large part to the ions presentin the solution.

The terms “conductivity meter,” “conductivity sensor,” “conductivitydetector” and the like refer to devices for measuring the electricalconductance of a solution and/or the ion, such as a sodium ion,concentration of a solution. In specific examples, the conductivitysensor, meter, or detector can be directed to a specific ion such assodium and be referred to as a “sodium electrode,” “sodium sensor,”“sodium detector,” or “sodium meter.”

The term “conduit,” “circuit” or “flow path” refers to a vessel orpassageway having a void volume through which a fluid can travel ormove. A conduit can have a dimension parallel to the direction of travelof the fluid that is significantly longer than a dimension orthogonal tothe direction of travel of the fluid

The term “connectable” refers to being able to be joined together forpurposes including but not limited to maintaining a position, allowing aflow of fluid, performing a measurement, transmitting power, andtransmitting electrical signals. The term “connectable” can refer tobeing able to be joined together temporarily or permanently.

The term “consisting of” includes and is limited to whatever follows thephrase “consisting of.” Thus, the phrase indicates that the limitedelements are required or mandatory and that no other elements may bepresent.

The term “consisting essentially of” includes whatever follows the term“consisting essentially of” and additional elements, structures, acts orfeatures that do not affect the basic operation of the apparatus,structure or method described.

The term “consumables” refers to components that are dissipated, wasted,spent or used up during the performance of any function in the presentinvention. Examples include a quantity of sodium, bicarbonate,electrolytes, infusates, sorbents, cleaning and disinfectingingredients, anticoagulants, and components for one or more concentratesolutions.

The terms “consumables cartridge” and “consumables container” refer toan object or apparatus having or holding one or more materials that aredepleted during operation of the system. The one or more materials maybe in solid and/or solution form and can be in separate compartments ofthe object or apparatus. The object or apparatus may be single use, ormay be replenished and used multiple times, for example, by refillingthe object to replace the consumed material.

The term “contact” “contacted” or “contacting” refers to (1) a comingtogether or touching of objects, fluids, or surfaces; (2) the state orcondition of touching or of immediate proximity; (3) connection orinteraction. For example, in reference to a “dialysate contacting asorbent material” refers to dialysate that has come together, hastouched, or is in immediate proximity to connect or interact with anymaterial or material layer of a sorbent container, system or cartridge.

The term “container” as used herein is a receptacle that may be flexibleor inflexible for holding any fluid or solid, such as for example aspent dialysate fluid, or a sodium chloride or sodium bicarbonatesolution or solid, or the like.

The term “contaminant” refers to an undesirable or unwanted substance ororganism that may cause impairment of the health of a subject receivinga treatment or of the operation of the system.

The term “control pump,” such as for example an “ultrafiltrate pump,”refers to a pump that is operable to pump fluid bi-directionally toactively control the transfer of fluid volume into or out of acompartment or circuit.

The terms “control reservoir,” “ultrafiltrate reservoir,” “solutionreservoir,” “therapy solution reservoir,” or “waste reservoir” can referto a vessel or container, optionally accessible by a control pump thatcontains a variable amount of fluid, including fluid that can bereferred to as an ultrafiltrate. These reservoirs can function as acommon reservoir to store fluid volume from multiple sources in asystem. Other fluids that can be contained by these reservoirs include,for example, water, priming fluids, waste fluids, dialysate, includingspent dialysate, and mixtures thereof. In certain embodiments, thereservoirs can be substantially inflexible, or non-flexible. In otherembodiments, the reservoirs can be flexible containers such as a polymerbag.

The term “control signals” refers to energy that is provided from oneelement of a system to another element of a system to convey informationfrom one element to another or to cause an action. For example, acontrol signal can energize a valve actuator to cause a valve to open orclose. In another example a switch on a valve can convey the open orclose state of a valve to a controller.

A “control system” consists of combinations of components that acttogether to maintain a system to a desired set of performancespecifications. The control system can use processors, memory andcomputer components configured to interoperate to maintain the desiredperformance specifications. It can also include fluid control componentsand solute control components as known within the art to maintain theperformance specifications

The term “control valve” or “valve” refers to a device that can beoperated to regulate the flow of fluid through a conduit or flow path byselectively permitting fluid flow, preventing fluid flow, modifying therate of fluid flow, or selectively guiding a fluid flow to pass from oneconduit or flow path to one or more other conduits or flow paths.

The terms “controlled compliance” and “controlled compliant” describethe ability to actively control the transfer of fluid volume into or outof a compartment, flow path or circuit. In certain embodiments, thevariable volume of fluid in a dialysate circuit controlled or compliantflow path expands and contracts via the control of one or more pumps inconjunction with one or more reservoirs. The volume of fluid in thesystem is generally constant (unless additional fluids are added to areservoir from outside of the system) once the system is in operation ifthe patient fluid volume(s), flow paths, and reservoirs are consideredpart of the total volume of the system (each individual volume maysometimes be referred to as a fluid compartment). The attachedreservoirs allow the system to adjust the patient fluid volume bywithdrawing fluid and storing the desired amount in an attached controlreservoir and/or by providing purified and/or rebalanced fluids to thepatient and optionally removing waste products. The terms “controlledcompliance” and “controlled compliant” are not to be confused with theterm “non-compliant volume,” which simply refers to a vessel, conduit,container, flow path, conditioning flow path or cartridge that resiststhe introduction of a volume of fluid after air has been removed from adefined space such as a vessel, conduit, container, flow path,conditioning flow path or cartridge. In one embodiment, and as discussedherein and shown in the drawings is that the controlled compliant systemcan move fluids bi-directionally. In certain cases, the bi-directionalfluid movement is across a semi-permeable membrane either inside oroutside a dialyzer. The bi-directional fluid flow can also occur across,through, or between of vessels, conduits, containers, flow paths,conditioning flow paths or cartridges of the invention in selected modesof operation. The term “moving fluid bi-directionally” as used inconnection with a barrier, such as a semi-permeable membrane, refers tothe ability to move a fluid across the barrier in either direction.“Moving fluid bi-directionally” also can apply to the ability to movefluid in both directions in the flow path or between a flow path andreservoir in a controlled compliant system.

The terms “controlled compliant flow path”, “controlled compliantdialysate flow path” and “controlled compliant solution flow path” referto flow paths operating within a controlled compliant system having thecharacteristic of controlled compliance, or of being controlledcompliant as defined herein.

The term “controller,” “control unit,” “processor,” or “microprocessor”refers to a device which monitors and affects the operational conditionsof a given system. The operational conditions are typically referred toas output variables of the system wherein the output variables can beaffected by adjusting certain input variables.

The term “convective clearance” refers to the movement of solutemolecules or ions across a semi-permeable barrier due to force createdby solvent molecules moving across the semi-permeable barrier.

The terms “coordinately operates” and “coordinately operating” refer tocontrolling the function of two or more elements or devices so that thecombined functioning of the two or more elements or devices accomplishesa desired result. The term does not exclusively imply that all suchelements or devices are simultaneously energized.

The term “de-aeration” refers to removing some or all of the aircontained in a liquid including both dissolved and non-dissolved aircontained in the liquid.

The term “de-aeration flow path” or “de-aeration flow circuit” refers toa set of elements that are configured in fluid communication along afluid flow pathway such a liquid can be passed through the fluid flowpathway to accomplish removal of some or all of the air or gas containedin the liquid, including removal of air or gas that is dissolved in theliquid.

The term “degas module” or “degassing module” refers to a component thatseparates and removes any portion of one or more dissolved orundissolved gas from a liquid. A degas module can include a hydrophobicmembrane for allowing ingress or egress of gases through a surface ofthe module while preventing the passage of liquid through that surfaceof the module.

The term “deionization resin” refers to any type of resin or materialthat can exchange one type of ion for another. In one specific case, theterm can refer to the removal of ions such as potassium, magnesium,sodium and calcium in exchange for hydrogen and/or sodium ions.

The term “detachable” refers to a characteristic of an object orapparatus that permits it to be removed and/or disconnected from anotherobject or apparatus.

The term “dialysate” describes a fluid into or out of which solutes froma fluid to be dialyzed diffuse through a membrane. A dialysate typicallycontains electrolytes that are close in concentration to thephysiological concentration of electrolytes found in blood. A commonsodium level for dialysate is ˜140 mEq/L. Normal blood sodium levelsrange from approximately 135 mEq/L to 145 mEq/L. The REDY systemtypically uses dialysate ranging from 120 mEq/L to 160 mEq/L. In certainembodiments, a “predetermined limit” or “predetermined concentration” ofsodium values can be based off the common sodium levels for dialysateand normal blood sodium levels.

The term “dialysate flow loop,” “dialysate flow path” or “dialysateconduit flow path” refers to any portion of a fluid pathway that conveysa dialysate and is configured to form at least part of a fluid circuitfor hemodialysis, hemofiltration, hemodiafiltration or ultrafiltration

The term “dialysate regeneration unit” or “dialysate regenerationsystem” refers to a system for removing certain electrolytes and wastespecies including urea from a dialysate after contact with a dialyzer.In certain instances, the component contained within the “dialysateregeneration unit” or “dialysate regeneration system” can decrease theconcentration or conductivity of at least one ionic species, or releaseand/or absorb at least one solute from a dialysate.

“Dialysis” is a type of filtration, or a process of selective diffusionthrough a membrane. Dialysis removes solutes of a specific range ofmolecular weights via diffusion through a membrane from a fluid to bedialyzed into a dialysate. During dialysis, a fluid to be dialyzed ispassed over a filter membrane, while dialysate is passed over the otherside of that membrane. Dissolved solutes are transported across thefilter membrane by diffusion between the fluids. The dialysate is usedto remove or add solutes from the fluid to be dialyzed. The dialysatecan also provide enrichment to the other fluid.

The terms “dialysis membrane,” “hemodialysis membrane,” “hemofiltrationmembrane,” “hemodiafiltration membrane,” “ultrafiltration membrane,” canoften generally be referred to as a “membrane,” or can refer to asemi-permeable barrier selective to allow diffusion and/or convection ofsolutes between blood and dialysate, or blood and filtrate, of aspecific range of molecular weights in either direction through thebarrier that separates blood and dialysate, or blood and filtrate, whileallowing diffusive and/or convective transfer between the blood on oneside of the membrane and the dialysate or filtrate circuit on the otherside of the membrane.

The term “dialyzer” refers to a cartridge or container with two flowpaths separated by semi-permeable membranes. One flow path is for bloodand one flow path is for dialysate. The membranes can be in the form ofhollow fibers, flat sheets, or spiral wound or other conventional formsknown to those of skill in the art. Membranes can be selected from thefollowing materials of polysulfone, polyethersulfone, poly(methylmethacrylate), modified cellulose, or other materials known to thoseskilled in the art.

The term “diluent” or “diluate” refers to a fluid having a concentrationof a specific species less than a fluid to which the diluent is added.

The term “disinfection fluid” refers to a solution for use in cleaningand disinfecting an apparatus for hemodialysis, hemodiafiltration orhemofiltration. The disinfection fluid may act thermally, chemically,and combinations thereof to inhibit growth of or to destroymicroorganisms. The “disinfection fluid” may further act to remove, atleast in part, a buildup of microorganisms on a surface of a fluid flowpath, such buildups of microorganisms may be commonly referred to as abiofilm.

The terms “disposable” and “disposables” refer to any component that issuitable for one or multiple use, but requires replacement orrefurbishment. Non-limiting examples include a disposable dialyzer, ureasensors, and a degassing module. Disposables can also mean componentsthat have a limited life such as microbial filters, containers,replaceable reservoirs and the like.

The term “downstream” refers to a relative position in which componentsof the device or fluid have moved relative to which the dialysate orother fluid has moved within a conduit or flow path.

The term “downstream conductivity” refers to the conductivity of a fluidsolution as measured at a location of a fluid flow path in the directionof the normal fluid flow from a reference point.

The term “drain connection” refers to being joined in fluidcommunication with a conduit or vessel that can accept fluid egress fromthe system.

The term “dry” as applied to a solid or a powder contained in acartridge means not visibly wet, and may refer interchangeably toanhydrous and also to partially hydrated forms of those materials, forexample, monohydrates and dihydrates.

The term “dry composition” refers to a compound that does not contain asubstantial quantity of water and can include anhydrous forms as well ashydrates for example, monohydrates and dihydrates.

The term “effluent dialysate,” as used herein describes the discharge oroutflow from a dialyzer after the dialysate has been used for dialysis.

The term “electrode” as used herein describes an electrical conductorused to make contact with a part of a fluid, a solid or solution. Forexample, electrical conductors can be used as electrodes to contact anyfluid (e.g. dialysate) to measure the conductivity of the fluid ordeliver or receive charge to the fluid.

The term “electrolyte” refers to an ion or ions dissolved in an aqueousmedium, including but not limited to sodium, potassium, calcium,magnesium, acetate and chloride.

The term “electrolyte source” “electrolyte source” refers to a storedsubstance that provides one or more electrolytes

The terms “equilibrated,” “equilibrate,” “to equilibrate,” and the likerefer to a state where a concentration of a solute in a first fluid hasbecome approximately equal to the concentration of that solute in thesecond fluid. However, the term equilibrated as used herein does notimply that the concentration of the solute in the first fluid and thesecond fluid have become equal. The term can also be used in referenceto the process of one or more fluids coming into equilibrium where thefluids have equal pressures, such as between a liquid and a gas.

The terms “equilibrated,” “equilibrate,” “to equilibrate,” and the likerefer to a state where a concentration of a solute in a first fluid hasbecome approximately equal to the concentration of that solute in thesecond fluid. However, the term equilibrated as used herein does notimply that the concentration of the solute in the first fluid and thesecond fluid have become equal. The term can also be used in referenceto the process of one or more gases coming into equilibrium where thegases have equal pressures or between a liquid and a gas.

The phrase “equilibrated to the solute species concentration” refers toa concentration of a particular solute species in a first fluid that hasbecome approximately equal to the concentration of that solute speciesin the second fluid. The concentration need not be exact.

The terms “evacuation volume”, “priming volume” and “void volume” referto the internal volume of a component or collection of componentscomprising a fluid flow path and are the volume of fluid that can beremoved from the fluid flow path to empty the fluid flow path if it hasbeen filled with fluid.

The term “extracorporeal,” as used herein generally means situated oroccurring outside the body.

The term “extracorporeal circuit” or “extracorporeal flow path” refersto a fluid pathway incorporating one or more components such as but notlimited to conduits, valves, pumps, fluid connection ports or sensingdevices configured therein such that the pathway conveys blood from asubject to an apparatus for hemodialysis, hemofiltration,hemodiafiltration or ultrafiltration and back to the subject.

The terms “extracorporeal flow path pump” and “blood pump” refer to adevice to move or convey fluid through an extracorporeal circuit. Thepump may be of any type suitable for pumping blood, including thoseknown to persons of skill in the art, for example peristaltic pumps,tubing pumps, diaphragm pumps, centrifugal pumps, and shuttle pumps.

The terms “filtrate regeneration unit” and “filtrate regenerationsystem” refer, in context, to a system for removing certain electrolytesand waste species including urea from a filtrate produced usingfiltration.

The terms “filtrate regeneration circuit”, “filtrate regeneration loop”,and the like, refer to a flow path containing fluid resulting fromfiltration; for the removal of certain electrolytes and waste speciesincluding urea.

The term “filtration” refers to a process of separating solutes from afluid, by passing the fluid through a filter medium across which certainsolutes or suspensions cannot pass. Filtration is driven by the pressuredifference across the membrane.

The term “first terminal end” of a flow path refers to one end of theflow path and “second terminal end” refers to another end of the flowpath. Neither the “first terminal end” nor the “second terminal end” hasany limitation on placement on an arterial or venous side.

The term “first terminal valve” refers to a valve substantially locatedat one end of a first fluid conduit without any requirement that thevalve be place on an arterial or venous side. Similarly, the term“second terminal valve” refers to a valve substantially located at oneend of a second fluid conduit and so on without any limitation onplacement on an arterial or venous side

The term “flow loop” refers to a grouping of components that may guidethe movement of a fluid, convey the fluid, exchange energy with thefluid, modify the composition of the fluid, measure a characteristic ofthe fluid and/or detect the fluid. A flow loop comprises a route or acollection of routes for a fluid to move within. Within a flow loopthere may be more than one route that a volume of fluid can follow tomove from one position to another position. A fluid volume may movethrough a flow loop such that it recirculates, or passes the sameposition more than once as it moves through a flow loop. A flow loop mayoperate to cause fluid volume ingress to and fluid volume egress fromthe flow loop. The term “flow loop” and “flow path” often may be usedinterchangeably. Further types of flow paths may be further defined; forexample, (1) a recirculation flow path, would be a flow path whosefunction is in whole or part is to recirculate fluid through the definedflow path; (2) a dialyzer recirculation flow path would be a flow pathwhose function is in whole or part is to recirculate fluid through thedefined flow path having a dialyzer’ (3) a controlled compliant flowpath would be a flow path would be a flow path that is controlledcompliant as defined herein. Any of the defined flow paths may bereferred to numerically, as a first flow path, second, third flow path,or fourth flow path, and the like flow paths.

The term “flow path” refers to a route or a collection of routes for afluid to move within. Within a flow path there may be more than oneroute that a fluid can follow to move from a first position to a secondposition. A fluid may move through a flow path such that itrecirculates, or passes the same position more than once as it movesthrough a flow path. A flow path may be a single element such as a tube,or a flow path may be a grouping of components of any type that guidethe movement of a fluid. The term “flow loop” and “flow path” often maybe used interchangeably.

The terms “flow restriction” and “flow restriction device” and “flowrestrictor” refer to an element or grouping of elements that resist theflow of fluid through the element or grouping of elements such that thefluid pressure within a flow stream that passes through the element orgrouping of elements is greater upstream of the element or grouping ofelements than downstream of the element or grouping of elements. A flowrestrictor may be an active or passive device. Non-limiting examples ofpassive flow restriction devices are orifices, venturis, a narrowing, ora simple length of tubing with flow cross section that produces thedesired pressure drop when the fluid flows through it, such tubing beingessentially rigid or compliant. Non-limiting examples of active flowrestrictors are pinch valves, gate valves and variable orifice valves.The term “flow stream” refers to fluid moving along a flow path.

The term “fluid balance control pump” refers to where a control pump isused to adjust the concentration or amount of a solute or fluid in thesystem. For example, a fluid balance control pump is used forselectively metering in or selectively metering out a designated fluidwherein the concentration or amount of a solute or fluid is adjusted

The term “fluid communication” refers to the ability of fluid to movefrom one part, element, or component to another; or the state of beingconnected, such that fluid can move by pressure differences from oneportion that is connected to another portion.

The term “fluid port” refers to an aperture through which a liquid orgas can be conveyed.

The term “fluid port cap or plug” refers to a device that can beconnected to a fluid port to prevent fluid from passing through thefluid port. A fluid cap or plug may be configured into an apparatushaving multiple caps or plugs to prevent fluid from passing throughmultiple fluid ports when the apparatus is connected to the multiplefluid ports.

The term “fluid port jumper” refers to a device that can be connectedbetween two or more fluid ports to enable a fluid to move between thetwo or more fluid ports by passing through the device. A fluid portjumper can be a discrete tube or conduit. Multiple fluid port jumperscan be arranged into an assembly such as a cleaning manifold.

The term “flush reservoir” is used to describe a container that canaccept or store fluid that is removed from the system during rinsing orcleaning of fluid pathways of the system, including draining the systemafter cleaning and/or disinfection has been completed.

The term “gas port” refers to an aperture through which any gaseous formof matter can be conveyed.

“Gas phase pressure” also known as “vapor” is the equilibrium pressurefrom a liquid or a solid at a specific temperature. If the vapor is incontact with a liquid or solid phase, the two phases will be in a stateof equilibrium.

“Hemodiafiltration” is a therapy that combines hemofiltration andhemodialysis.

“Hemodialysis” is a technique where blood and a “cleansing fluid” calleddialysate are exposed to each other separated by a semi-permeablemembrane. Solutes within the permeability range of the membrane passwhile diffusing along existing concentration gradients. Water andsolutes are also transferred by convection across a pressure gradientthat may exist across the dialysis membrane. The dialysate employedduring hemodialysis has soluble ions such as sodium, calcium andpotassium ions and is not pure water. The sieving properties of themembrane exclude certain solutes above a certain threshold from crossingthe membrane. One common sieving property is “albumin sieving.” In mostsituations it is not desirable to remove albumin during renalreplacement therapy, as lower blood serum albumin is associated withincreased mortality rates.

The term “hemofilter” refers to a apparatus (or may refer to a filter)used in hemofiltration. A hemofilter apparatus can be connected to anextracorporeal circuit and configured to operate with a semipermeablemembrane that separates at least a portion of the fluid volume fromblood to produce a filtrate fluid.

“Hemofiltration” is a therapy in which blood is filtered across asemi-permeable membrane. Water and solutes are removed from the bloodvia pressure-driven convection across the membrane. The sievingproperties of the membrane exclude certain solutes above a certainthreshold from crossing the membrane. One common sieving property is“albumin sieving.” In most situations it is not desirable to removealbumin during renal replacement therapy, as lower blood serum albuminis associated with increased mortality rates. In hemofiltration, solutessmall enough to pass through the membrane in proportion to their plasmaconcentration are removed. The driving force is a pressure gradientrather than a concentration gradient. A positive hydrostatic pressuredrives water and solutes across the filter membrane from the bloodcompartment to the filtrate compartment, from which it is drained.Solutes, both small and large, get dragged through the membrane at asimilar rate by the flow of water that has been engineered by thehydrostatic pressure. Hence, convection overcomes the reduced removalrate of larger solutes (due to their slow speed of diffusion) observedin hemodialysis. The rate of solute removal is proportional to theamount of fluid removed from the blood circuit, which can be adjusted tomeet the needs of a clinical situation. In general, the removal of largeamounts of plasma water from the patient requires volume substitution.Substitution fluid, typically a buffered solution close to the plasmawater composition a patient needs, can be administered pre or postfilter (pre-dilution mode, post-dilution mode).

The term “hydrophobic membrane” refers to a semipermeable porousmaterial that may allow gas phases of matter to pass through, but whichsubstantially resists the flow of water through the material due to thesurface interaction between the water and the hydrophobic material.

The terms “hydrophobic vent” and “hydrophobic vent membrane” refer to aporous material layer or covering that can resist the passage of aliquid such as water through the pores while allowing the passage of agas. The pores may also be of a sufficiently small size to substantiallyprevent the passage of microorganisms.

The term “impedance meter” refers to a device for measuring theopposition of an object or structure to an alternating current.

The terms “impurity”, or “impurity species” refer to a molecular orionic species that originates from tap water, a sorbent cartridge, asource other than a patient's or the subject's blood including, forexample, but limited to chlorine, fluoride ions, and aluminum-containingspecies. The term “impurity species” can also refer to solutes in ablood that are in too high of a concentration in the blood from standardranges known in the art or that are solutes that have resulted frommetabolism to generate a non-healthy component now residing in theblood. In certain instances, an “impurity species” can also be regardedas a “waste species,” or “waste products.”

The terms “infusate container” and “infusate reservoir” refer to avessel, which can be substantially flexible or non-flexible for holdinga solution, for example a solution of one or more salts, for theadjustment of the composition of a dialysate.

The term “infusate solution” refers to a solution of one or more saltsor chemicals for the adjustment of the composition of a dialysate, suchas salts of calcium, magnesium and potassium, and glucose.

The term “infusate system” refers to a system that incorporates at leastone fluid pathway including components such as conduits, valves, pumpsor fluid connection ports, an infusate container or a controllerconfigured to add an infusate solution to a dialysate.

The term “interchangeable bicarbonate cartridge” refers to a bicarbonatecartridge that can be configured for removal and replacement with a likebicarbonate cartridge. Interchangeable bicarbonate cartridges can besingle use disposable, or re-fillable, re-usable containers.

The term “interchangeable sodium chloride cartridge” refers to a sodiumchloride cartridge that can be configured for removal and replacementwith a like sodium chloride cartridge. Interchangeable sodium chloridecartridges can be single use disposable, or re-fillable, re-usablecontainers.

The terms “introduce” and “introducing” refer to causing a substance tobecome present where it was not present, or to cause the amount orconcentration of a substance to be increased.

The term “ion-exchange material” refers to any type of resin or materialthat can exchange one type of ion for another. The “ion-exchangematerial” can include anion and cation exchange materials. In onespecific case, the term can refer to the removal of ions such aspotassium, magnesium, sodium, phosphate and calcium in exchange forother ions such as potassium, sodium, acetate, hydrogen and/orhydroxide.

An “ion-exchange resin” or “ion-exchange polymer” is an insoluble matrix(or support structure) that can be in the form of small (1-2 mmdiameter) beads, fabricated from an organic polymer substrate. Thematerial has a developed structure of pores on the surface of which aresites with easily trapped and released ions. The trapping of ions takesplace only with simultaneous releasing of other ions; thus the processis called ion-exchange. There are multiple different types ofion-exchange resins which are fabricated to selectively prefer one orseveral different types of ions. In one specific case, the term canrefer to the removal of ions such as potassium, magnesium, sodium,phosphate and calcium in exchange for other ions such as potassium,sodium, acetate, hydrogen and/or hydroxide.

The term “ion selective electrode” refers to electrodes coated with amaterial that only allows certain ions to pass through. An “ionselective electrode” (ISE), also known as a specific ion electrode(SIE), is a transducer (or sensor) that converts the activity of aspecific ion dissolved in a solution into an electrical potential, whichcan be measured by a voltmeter or pH meter. The voltage is theoreticallydependent on the logarithm of the ionic activity, according to theNernst equation. The sensing part of the electrode is usually made as anion-specific membrane, along with a reference electrode.

The term “jumper” refers to a fluid conduit that completes a fluidpathway at least between two or more points of connection within a fluidcircuit. The term “jumper” is not limited to a tube shaped item, but maybe any component or arrangement of components that allows fluid to passfrom at least a first point of connection to at least a second point ofconnection.

The term “jumpered port” refers to any connection opening that may beconnected to another connection opening by an intermediate component orgrouping of components to allow a fluid flow to occur between the saidconnection openings. The jumpered port can be configured to interfacewith a fluid conduit, pathway or passageway external to a unit or modulehaving the jumpered port. The term “jumpered port” is intended to beinterpreted in its broadest sense and encompasses any facilitation offluid from one flow path or segment of a flow path to another using anyof holes, fittings, fixtures, outlet, inlet, orifice, connectors,couplings, junctions or the like.

The term “junction” refers to a common point of connection between twoor more flow paths or conduits that allows a liquid and/or a gas to movefrom one pathway or conduit to another. A junction may be a reversibleconnection that can be separated when transfer of a liquid and/or gasbetween the flow paths or conduits is not needed

The term “kidney replacement therapy” as used herein describes the useof a provided system to replace, supplement, or augment the function ofa patient with impaired kidney function, such as would occur for apatient with Chronic Kidney Disease. Examples of kidney replacementtherapy would include dialysis, hemofiltration, hemodialysis,hemodiafiltration, peritoneal dialysis, and the like.

The term “luer connector” or “luer adapter” refers to adapters orconnectors conforming to International Standards Organization (ISO)standards 594-2.

The term “manifold” refers to a collection of one or more fluid pathwaysthat are formed within a single unit or subassembly. Many types ofmanifolds can be used, e.g. a cleaning and/or disinfecting manifold isused to clean or disinfect the defined flow loop when the flow loop isconnected to the cleaning and/or disinfecting manifold.

The term “material layer” refers to the layers of materials found in asorbent cartridge. The material layers in a sorbent cartridge may haveone or more layers selected from a urease-containing material, alumina,zirconium phosphate, zirconium oxide, and activated carbon.

The term “memory” refers to a device for recording digital informationthat can be accessed by a microprocessor, such as RAM, Dynamic RAM,microprocessor cache, FLASH memory, or memory card.

The term “metabolic waste species,” as used herein describes organic andinorganic components generated by a patient. They can be metabolicproducts such as urea, uric acid, creatinine, chlorides, inorganicsulfates and phosphate, or excess electrolytes such as sodium,potassium, etc. It will be understood that the specific “metabolic wastespecies” can vary between individuals depending on diet andenvironmental factors. Hence, the term is intended to encompass anywaste component that is normally removed by a kidney or by dialysiswithout restriction on the specific type of waste substance.

The term “microbial filter” refers to a device configured to inhibit thepassage of microbes or fragments of microbes such as endotoxins conveyedby a fluid or solution while allowing the passage of the fluid orsolution.

The term “mid-weight uremic wastes” refers to substances that can passthrough a dialysis membrane and have a molecular weight less than about66,000 g/mol and greater than about 1000 g/mol. An example of a middlemolecule is beta-2 microglobulin.

The term “moving fluid bi-directionally” as used in connection with abarrier, such as a semi-permeable membrane, refers to the ability tomove a fluid across the barrier in either direction. “Moving fluidbi-directionally” also can apply to the ability to move fluid in bothdirections in the flow loop in a controlled compliant system.

The term “nitrogenous waste” refers to any non-polymericnitrogen-containing organic compound originating from the blood of apatient. Nitrogenous waste includes urea and creatinine, which are both“waste species.”

The term “one-way valve” refers to a device that allows flow to pass inone direction through the valve, but prevents or substantially resistsflow through the valve in the opposite direction. Such devices caninclude devices commonly referred to as check valves.

The term “osmolarity” is defined as the number of osmoles of a soluteper liter of solution. Thus, a “hyperosmolar solution” represents asolution with an increase in osmolarity compared to physiologicsolutions. Certain compounds, such as mannitol, may have an effect onthe osmotic properties of a solution as described herein.

The term “parallel or wound hollow fiber assembly” refers to any devicethat incorporates a porous or non-porous hollow fiber material thatallows a gas to pass through the material wall of the hollow fibers, butresists the passage of a liquid through the material wall and isconfigured as multiple strands aligned in parallel or wrapped around acore. The liquid to be degassed may be conveyed through either theinside of the hollow fibers or around the outside of the hollow fibers.Optionally, a gas may be conveyed on the side of the material wall thatis opposite the liquid to be degassed. Optionally, a vacuum may beapplied on the side of the material wall that is opposite the liquid tobe degassed.

The terms “pathway,” “conveyance pathway” and “flow path” refer to theroute through which a fluid, such as dialysate or blood travels.

A “patient” or “subject” is a member of any animal species, preferably amammalian species, optionally a human. The subject can be an apparentlyhealthy individual, an individual suffering from a disease, or anindividual being treated for a disease.

The term “patient fluid balance” refers to the amount or volume of fluidadded to or removed from a subject undergoing a treatment.

The term “peristaltic pump” refers to a pump that operates bycompression of a flexible conduit or tube through which the fluid to bepumped passes.

“Peritoneal dialysis” is a therapy wherein a dialysate is infused intothe peritoneal cavity, which serves as a natural dialyzer. In general,waste components diffuse from a patient's bloodstream across aperitoneal membrane into the dialysis solution via a concentrationgradient. In general, excess fluid in the form of plasma water flowsfrom a patient's bloodstream across a peritoneal membrane into thedialysis solution via an osmotic gradient.

The term “physiologically compatible fluid” or “physiological compatiblesolution” refers to a fluid that can be safely introduced into thebloodstream of a living subject.

The term “plumbing,” as used herein generally describes any system ofvalves, conduits, channels, and lines for supplying and directing any ofthe fluids used in the invention.

The term “priming process” refers to the process of conveying a liquidinto the void volume of a fluid pathway to fill the pathway with liquid.

The term “porosity,” as used herein describes the fraction of open porevolume of a membrane.

The terms “portable system” or “wearable system” refers to a system inwhole or in part having a mass and dimension to allow for transport by asingle individual by carrying the system or wearing the system on theindividual's body. The terms are to be interpreted broadly without anylimitation as to size, weight, length of time carried, comfort, ease ofuse, and specific use by any person whether man, woman or child. Theterm is to be used in a general sense wherein one of ordinary skill willunderstand that portability as contemplated by the invention encompassesa wide range of weights, geometries, configurations and size.

The term “potable water” refers to drinking water or water that isgenerally safe for human consumption with low risk of immediate or longterm harm. The level of safety for human consumption can depend on aparticular geography where water safe for human consumption may bedifferent from water considered safe in another jurisdiction. The termdoes not necessarily include water that is completely free ofimpurities, contaminants, pathogens or toxins. Other types of watersuitable for use in the present invention can include purified,deionized, distilled, bottled drinking water, or other pre-processedwater that would be understood by those of ordinary skill in the art asbeing suitable for use in dialysis

The term “prefilled” refers to a substance that has been added inadvance.

The terms “pressure differential” and “pressure drop” refer to thedifference in pressure measurements of a fluid between two points ofmeasurement.

The terms “pressure meter” and “pressure sensor” refer to a device formeasuring the pressure of a gas or liquid in a vessel or container.

The term “priming fluid” refers to a liquid that can be used to displacegas from a flow path.

The term “priming overflow reservoir” refers to a reservoir which duringpriming is used to collect the overflow of fluid during the primingprocess.

The term “priming process” or “priming” refers to the process ofconveying a liquid into the void volume of a fluid pathway to fill thepathway with liquid.

The term “priming volume” refers to the volume of priming fluid requiredto fill the void volume of the subject pathway, device, or component, asthe particular case may be.

The terms “processor,” “computer processor,” and “microprocessor” asused herein are broad terms and are to be given their ordinary andcustomary meaning to a person of ordinary skill in the art. The termsrefer without limitation to a computer system, state machine, processor,or the like designed to perform arithmetic or logic operations usinglogic circuitry that responds to and processes the basic instructionsthat drive a computer. In some embodiments, the terms can include ROM(“read-only memory”) and/or RAM (“random-access memory”) associatedtherewith.

The term “programmable” as used herein refers to a device using computerhardware architecture with a stored program and being capable ofcarrying out a set of commands, automatically that can be changed orreplaced.

The term “pulsatile pump” refers to a pump where the pumped fluidundergoes periodic variation in velocity and/or pressure.

The term “pump” refers to any device that causes the movement of fluidsor gases by the application of suction or pressure.

The terms “pump rate” and “volumetric pumping rate” refer to the volumeof fluid that a pump conveys per unit of time.

The term “purified water” refers to water that has been physicallyprocessed to remove at least a portion of at least one impurity from thewater.

The terms “reconstitute” or “reconstituting” refer to creating asolution by addition of a liquid to a dry material or to a solution ofhigher concentration to change the concentration level of the solution.

The term “refilled” refers to having replenished or restored a substancethat has been consumed or degraded.

The term “remnant volume” or “residual volume” refers to the volume offluid remaining in a fluid flow path after the fluid flow path has beenpartially emptied or evacuated.

The terms “replacement fluid” and “substitution fluid” refer to fluidthat is delivered to the blood of a subject undergoing convective renalreplacement therapies such as hemofiltration or hemodiafiltration inorder to replace at least a portion of the fluid volume that is removedfrom the subject's blood when the blood is passed through a hemofilteror a dialyzer.

The term “replenished” refers to having refilled or restored a substancethat has been consumed or degraded.

The term “reserve for bolus infusion” refers to an amount of solutionavailable, if needed, for the purpose of administering fluid to asubject receiving therapy, for example, to treat an episode ofintradialytic hypotension.

The term “reusable” refers to an item that is used more than once.Reusable does not imply infinitely durable. A reusable item may bereplaced or discarded after multiple uses.

The term “reversible connections” refers to any type of detachable,permanent or non-permanent connection configured for multiple uses.

The term “salination pump” refers to a pump configured to move fluidand/or control movement of fluid through a conditioning flow path, suchas through or from a source of a conditioning material such as sodiumchloride or sodium bicarbonate.

The term “salination valve” refers to a valve configured to control theflow of fluid in a conditioning flow path, such as through or from asource of a conditioning material such as sodium chloride or sodiumbicarbonate.

The term “segment” refers to a portion of the whole, such as a portionof a fluid flow path or a portion of a fluid circuit. A segment is notlimited to a tube or conduit, and includes any grouping of elements thatare described for a particular segment. Use of the term “segment”, byitself, does not imply reversible or detachable connection to anothersegment. In an embodiment, a segment may be permanently connected to oneor more other segments or removably or detachably connected to one ormore segments.

The terms “selectively meter fluid in” or “selectively meter fluid out”generally refer to a process for controllably transferring fluids fromone fluid compartment (e.g. a selected patient fluid volume, flow path,or reservoir) to another fluid compartment. One non-limiting example iswhere a control pump may transfer a defined fluid volume container,reservoirs, flow paths, conduit of the controlled compliant system. Whenfluid is moved from a reservoir into another part of the system, theprocess is referred to as “selectively metering fluid in” as related tothat part of the system. Similarly, one non-limiting example of removingspent dialysate from a dialysate flow path in a controlled compliantsystem and storing the spent dialysate in a control reservoir, wherein adefined volume of the spent dialysate is transferred to a reservoir,such as a control reservoir can be referred to as “selectivelymetering-out” the fluid from the dialysate flow path.

The term “semipermeable membrane,” also termed a “selectively permeablemembrane,” a “partially permeable membrane,” or a “differentiallypermeable membrane,” is a membrane that will allow certain molecules orions to pass through it by diffusion and occasionally specialized“facilitated diffusion.” The rate of passage depends on the pressure,concentration, and temperature of the molecules or solutes on eitherside, as well as the permeability of the membrane to each solute. Theterm “semi-permeable membrane” can also refer to a material thatinhibits the passage of larger molecular weight components of a solutionwhile allowing passage of other components of a solution having asmaller molecular weight. For example, Dialyzer membranes come withdifferent pore sizes. Those with smaller pore size are called “low-flux”and those with larger pore sizes are called “high-flux.” Some largermolecules, such as beta-2-microglobulin, are not effectively removedwith low-flux dialyzers. Because beta-2-microglobulin is a largemolecule, with a molecular weight of about 11,600 daltons, it does notpass effectively through low-flux dialysis membranes.

The term “sensor,” which can also be referred to as a “detector” incertain instances, as used herein can be a converter that measures aphysical quantity of a matter in a solution, liquid or gas, and canconvert it into a signal which can be read by an electronic instrument.

The term “sensor element” refers to a device or component of a systemthat detects or measures a physical property.

The term “shunt,” as most often used herein describes a passage betweenchannels, in the described filtration and purification systems, whereinthe shunt diverts or permits flow from one pathway or region to another.An alternate meaning of “shunt” can refer to a pathway or passage bywhich a bodily fluid (such as blood) is diverted from one channel,circulatory path, or part to another. At times the term “bypass” maybeused interchangeable with the term “shunt.”

The term “sodium source” refers to a source from which sodium can beobtained. For example, the sodium source can be a solution containingsodium chloride or a dry sodium chloride composition that is hydrated bythe system.

The terms “sodium chloride cartridge” and “sodium chloride container”refer to an object that can be a stand-alone enclosure or alternativelycan be integrally formed with an apparatus for hemodialysis,hemodiafiltration, or hemofiltration. The object can store a source ofsodium, such as sodium chloride in solid and/or solution form, and canbe configured to interface with at least one other functional modulefound in systems for hemodialysis, hemodiafiltration, or hemofiltration.For example, the sodium chloride cartridge or container can contain atleast one fluid pathway and include components such as conduits, valves,filters or fluid connection ports.

The term “sodium conduit flow path” refers to a flow path in fluidcommunication with a sodium chloride cartridge which then can pumpsaturated sodium solution into the dialysate by pumping and meteringaction of a salination pump.

The term “sodium source” refers to a source from which sodium can beobtained. For example, the sodium source can be a solution containingsodium chloride or a dry sodium chloride composition that is hydrated bythe system

The term “solid bicarbonate” refers to a composition containing a saltof bicarbonate such as sodium bicarbonate at any purity level. Ingeneral, the solid bicarbonate will be easily soluble in water to form asolution.

The term “solute” refers to a substance dissolved, suspended, or presentin another substance, usually the component of a solution present in thelesser amount.

The term “solution regeneration system” refers to one or more sorbentmaterials for removing specific solutes from solution, such as urea.“Solution regeneration system” includes configurations where at leastsome of the materials contained in the system do not act by mechanismsof adsorption or absorption. The materials that comprise the solutionregeneration system may be configured in a single container or sorbentcartridge, or in separate containers or cartridges.

The terms “sorbent cartridge” and “sorbent container” interchangeablyrefer to an enclosure having one or more sorbent materials for removingspecific solutes from solution, such as urea. In certain embodiments,the term “sorbent cartridge” includes configurations where at least someof the materials contained in the cartridge do not act by mechanisms ofadsorption or absorption.

The terms “sorbent regeneration,” “sorbent regeneration system,”“sorbent system, and the like, refer, in context, to devices that arepart of a sorbent regenerated dialysate delivery system forhemodialysis, functioning as an artificial kidney system for thetreatment of patients with renal failure or toxemic conditions, and thatconsists of a sorbent cartridge and the means to circulate dialysatethrough this cartridge and the dialysate compartment of the dialyzer.The device is used with the extracorporeal blood system and the dialyzerof the hemodialysis system and accessories. The device may include themeans to maintain the temperature, conductivity, electrolyte balance,flow rate and pressure of the dialysate, and alarms to indicate abnormaldialysate conditions. The sorbent cartridge may include absorbent, ionexchange and catalytics.

The term “source of cations” refers to a source from which cations canbe obtained. Examples of cations include, but are not limited to,calcium, magnesium and potassium. The source can be a solutioncontaining cations or a dry composition that is hydrated by the system.The cation infusate source is not limited to cations and may optionallyinclude other substances to be infused into a dialysate or replacementfluid. Non-limiting examples include glucose, dextrose, acetic acid andcitric acid.

The term “specified gas membrane permeability” refers to a determinedrate at which a membrane will allow a gas to pass through the membranefrom a first surface to a second surface, the rate being proportional tothe difference in absolute pressure of the gas in proximity to the firstside of the membrane and in proximity to the second side of themembrane.

The term “spent dialysate” refers to a dialysate that has exchangedsolutes and/or water with blood through a dialysis membrane and containsone or more impurity, or waste species, or waste substance, such asurea.

The term “static mixer” refers to a device that mixes two or morecomponent materials in a fluid solution without requiring the use ofmoving parts.

The term “substantially inflexible volume” refers to a three-dimensionalspace within a vessel or container that can accommodate a maximum amountof non-compressible fluid and resists the addition of any volume offluid above the maximum amount. The presence of a volume of fluid lessthan the maximum amount will fail to completely fill the vessel orcontainer. Once a substantially inflexible volume has been filled with afluid, removal of fluid from that volume will create a negative pressurethat resists fluid removal unless fluid is added and removedsimultaneously at substantially equal rates. Those skilled in the artwill recognize that a minimal amount of expansion or contraction of thevessel or container can occur in a substantially inflexible volume;however, the addition or subtraction of a significant volume of fluidover a maximum or minimum will be resisted.

The term “tap water” refers to water, as defined herein, from a pipedsupply.

The term “temperature sensor” refers to a device that detects ormeasures the degree or intensity of heat present in a substance, object,or fluid.

The term “therapy cassette” refers to a detachable set of one or morecomponents that can be connected to an apparatus for performinghemodialysis, hemodiafiltration, or hemofiltration. A connection betweena therapy cassette and an apparatus may be for purposes including, butnot limited to, maintaining a position, allowing a flow of fluid,performing a measurement, transmitting power, and transmittingelectrical signals. A therapy cassette can incorporate at least onefluid pathway, and any one or combination of the following exemplary,non-limiting components such as conduits, fluid connection ports,concentrates, cartridges, valves, sensor elements, reservoirs, filters,vents, dialyzers, and disposable and consumable components. A therapycassette can be configured to interface with at least one other moduleof a dialysis apparatus such as a base module, to form at least onecomplete fluid circuit such as a controlled compliant flow path or ablood circuit for performing hemodialysis, hemodiafiltration, orhemofiltration. One or more components in a cassette can be anycombination of single use, disposable, consumable, replaceable, ordurable items or materials.

A ‘therapy solution reservoir” refers to any container or reservoir thatholds a physiological compatible fluid.

The terms “treating” and “treatment” refer to the management and care ofa patient having a pathology or condition by administration of one ormore therapy contemplated by the present invention. Treating alsoincludes administering one or more methods of the present invention orusing any of the systems, devices or compositions of the presentinvention in the treatment of a patient. As used herein, “treatment” or“therapy” refers to both therapeutic treatment and prophylactic orpreventative measures. “Treating” or “treatment” does not requirecomplete alleviation of signs or symptoms, does not require a cure, andincludes protocols having only a marginal or incomplete effect on apatient.

The term “ultrafiltrate” refers to fluid that is removed from a subjectby convection through a permeable membrane during hemodialysis,hemofiltration, hemodiafiltration, or peritoneal dialysis. The term“ultrafiltrate,” as used herein, can also refer to the fluid in areservoir that collects fluid volume removed from the patient, but sucha reservoir may also include fluids or collections of fluids that do notoriginate from the subject.

The term “ultrafiltration” refers to subjecting a fluid to filtration,where the filtered material is very small; typically, the fluidcomprises colloidal, dissolved solutes or very fine solid materials, andthe filter is a microporous, nanoporous, or semi-permeable medium. Atypical medium is a membrane. During ultrafiltration, a “filtrate” or“ultrafiltrate” that passes through the filter medium is separated froma feed fluid. In certain instances, the use of the term “filtrate” canrefer to the fluid generated during hemofiltration. In general, whentransport across a membrane is predominantly diffusive as a result of aconcentration driving force, the process is described herein asdialysis. When transport is primarily convective as a result of bulkflow across the membrane induced by a pressure driving force, theprocess is ultrafiltration or hemofiltration depending on the need forsubstitution solution as the membrane passes small solutes but rejectsmacromolecules. The term “ultrafiltration” can also refer to the fluidremoval from blood during a dialysis or a hemofiltration process. Thatis, ultrafiltration refers to the process of passing fluid through aselective membrane, such as a dialysis or hemofiltration membrane, indialysis, hemodiafiltration, or a filtration process.

The terms “unbuffered sodium bicarbonate” or “solution of unbufferedsodium bicarbonate” refer to a sodium bicarbonate composition that isnot buffered with a conjugate acid or base in any amount, proportion orpH adjustment.

The term “upper position” and “lower position” are relative terms toeach other wherein the upper position is at a higher elevation than thelower position.

The term “upstream” refers to a direction opposite to the direction oftravel of a moving dialysate or other fluid within a conduit or flowpath

The term “urea sensor” refers to a device for measuring or allowing forthe calculation of urea content of a solution. The “urea sensor” caninclude devices measuring urease breakdown of urea and measurement ofthe resulting ammonium concentration. The sensing methods can be basedon any one of conductimetric, potentiometric, thermometric,magnetoinductic, optical methods, combinations thereof and other methodsknown to those of skill in the art.

The term “uremic wastes” refers to a milieu of substances found inpatients with end-stage renal disease, including urea, creatinine,beta-2-microglobulin.

The term “user input surface” refers to a surface that incorporates auser interface incorporating one or more components such as a displayscreen, a keyboard, a mouse, a microphone, at least one speaker or atouch screen accessible by a human for communicating input data to anapparatus or a controller

The term “user interface module” refers to a device that incorporatesone or more components such as a display screen, a keyboard, a mouse, amicrophone, speaker or a touch screen configured to facilitatecommunication between a human and an apparatus or a controller

The term “vacuum” refers to an action that results from application of apressure that is less than atmospheric pressure, or negative to thereference fluid or gas

The term “vent” as referred to in relationship to a gas, refers topermitting the escape of a gas from a defined portion of the system,such as, for example, as would be found in the degassing module.

The term “void volume” refers to a specific volume that can be occupiedby a fluid in a defined space such as a controlled compliant flow pathof the invention including all components contained therein.

The term “waste fluid” refers to any fluid that does not have a presentuse in the operation of the system. Non-limiting examples of wastefluids include ultrafiltrate, or fluid volume that has been removed froma subject undergoing a treatment, and fluids that are drained or flushedfrom a reservoir, conduit or component of the system.

The term “waste species,” “waste products” or “impurity species” refersto any molecular or ionic species originating from the patient orsubject, including metabolic wastes, molecular or ionic speciesincluding nitrogen or sulfur atoms, mid-weight uremic wastes andnitrogenous waste. Waste species are kept within a specific homeostasisrange by individuals with a healthy renal system.

The term “water source” refers to a source from which potable or notpotable water can be obtained.

The term “water source connection” or “water feed” refers to a state offluid communication that enables water to be obtained from a watersource and connected or fed into a receiving source or flow path.

The term “within” when used in reference to the a sensor located“within” the sorbent cartridge refers to all or part of the electrode islocated inside or encased by at least part of the inner chamber formedfrom the sorbent cartridge wall.

The term “working dialysate solution” refers to a dialysate solutionthat is undergoing active circulation or movement through a systemincluding conduits, pathways, dialyzers and cartridges.

Modular Dialysis Systems with Jumpered Circuits

The therapy system and methods of the present invention can provide fordialysis therapy to be conducted remote from a high volume purifiedwater source and drain infrastructure and can be configured into amechanical package that will minimize the burden for system storage,transport, setup, operation, and routine maintenance. The presentinvention can further perform all functions necessary to conduct adialysis session, as well as routine cleaning and disinfectionmaintenance with input of only a limited volume of potable tap, orbottled drinking water or other suitable types of water that can be usedin any of hemodialysis, hemofiltration, hemodiafiltration and peritonealdialysis.

In some embodiments, the consumables can be configured within anintegrated therapy disposables and consumables cassette to simplifyequipment setup for a therapy session. A therapy cassette can have atleast one fluid pathway that is a part of a module or system forhemodialysis, hemodiafiltration, or hemofiltration. The cassette canhave one or more fluid pathways wherein connection to the module orsystem completes a controlled compliance dialysate flow path. It will beunderstood that a therapy cassette can contain any one or combination ofconduits for providing a flow path and fluid connection ports forconnecting a therapy cassette to the module. A therapy cassette can alsocontain any number of concentrates, cartridges, sensor elements,reservoirs, filters, vents to assist in the operation of the system. Thecassette can include dialyzers defined as “disposables” herein wherein adialyzer can be made integral to the therapy cassette or made fullyremovable. A fully detachable dialyzer wherein all functional componentsare removed from the therapy cassette are also contemplated by theinvention. A therapy cassette can contain consumable components asdefined herein such as sodium and salts thereof, bicarbonates and saltsthereof and other electrolytes and salts thereof. In certainembodiments, the inclusion of such consumable components is critical tothe invention by providing all necessary components for dialysis therapyin one module. A therapy cassette can have one consumable component suchas sodium or bicarbonate, or both. A therapy cassette may also containany number of sensors, plumbing and connections necessary to complete adialysate flow path between the therapy cassette and the base module orapparatus. In particular, a therapy cassette can be configured tointerface with at least one other module of a dialysis apparatus such asa base module, to form at least one complete fluid circuit such as acontrolled compliant flow path or a blood circuit for performinghemodialysis, hemodiafiltration, or hemofiltration.

In certain embodiments, the therapy disposable and consumable componentscan be advantageously configured into subgroupings to be installed on abase module, or even configured as individual components to be installedon a base module. When installed onto the base module, the flow pathscontained within individual or subgrouped components combine with thebase module to form a completed controlled compliance dialysate fluidcircuit for hemodialysis, hemodiafiltration, or hemofiltration. Suchconfigurations can be advantageous when it is desired to customize atherapy setup, for example, to use a particular dialyzer or acidconcentrate solution; or where economic preference favors re-use ofcertain components, such as in the case of refilling of a bicarbonateconsumables container.

The system prepares its own priming solution and conducts priming of thedialysate and extracorporeal flow paths automatically. A separate supplyof packaged or prepared sterile saline is not required for priming,fluid bolus, or blood rinse back when using this system. In certainembodiments, normal saline is around 0.9% by weight and is commonly usedfor priming dialyzers and extracorporeal circuits is 154 mEq/L. Certainportions of the dialysate circuit are re-used and routine cleaning anddisinfection maintenance of this fluid circuit is performedautomatically with a simple cleaning manifold. The system can beconfigured so that the cleaning manifold is stored and transportedin-situ and without opening the disinfected flow path. The system canalso be configured with design features that enable it to fold into asmall, self-protective form that may be readily transported by the user.In some embodiments, the space required for stowed transport orstationary storage is compatible with airline carry-on luggage sizeallowances. For example, in some, non-limiting embodiments, weights ofless than 15 kilograms and stowed configurations of less 40 litersvolume are contemplated by the present invention.

In the described controlled compliant flow path of the presentinvention, net passive movement of fluid volume across the dialysismembrane due to operational pressure changes is eliminated. Theinvention provides for the ability to accurately control net patientfluid removal, and/or diffusive clearance combined with increasedclearance via convection, and/or active provisioning of extra fluid to apatient. The system allows priming of the controlled compliant flow pathand extracorporeal flow path, a fluid bolus, or the return of blood fromthe system back to the patient without requirement to provide foradditional fluids from a separate source. The invention can activelyprovide fluid to the patient when the patient becomes hypotensive orhypovolemic, and can displace the internal volume of a blood circuitwith a physiological solution when a patient is taken off a system. Theinvention can also provide for actively enhanced convective clearance byalternately varying the rate and/or direction of the fluid balancecontrol pump. Any combination of the above mentioned features iscontemplated by the invention. The system can optionally account for aninfusate volume, provide additional convective clearance, and/or providecontrol of the entire process. The controlled compliant flow path canhave one or more means for selectively metering fluid into and out ofthe controlled compliant flow path. The means can be any one of controlpump, a water pump, a salination pump, an acid concentrate pump, andcombinations thereof and, in some cases, a replacement fluid pump. Thedescribed controlled compliant flow path also simplifies the entiresystem. Specifically, balance chambers, scales or gravimetric controlmethods are not required to balance fluid removal with fluidreplacement.

FIG. 1 shows a system for circulating blood and a dialysate through adialyzer 701. A shunt such as a needle or catheter is connected to apatient's vasculature to draw blood and circulate the patient's bloodthrough an extracorporeal flow path 100. The portion of theextracorporeal flow path 100 that contains drawn blood from the patientcan be referred to as the arterial line 102, which by convention isunderstood to mean a line for transporting blood from the patientregardless of whether blood is drawn from an artery or vein of thepatient. Similarly, the portion that returns blood to the patient can bereferred to as the venous line 105. In certain embodiments, the arterialline 102 and the venous line 105 connect with one or more veins of thepatient. Locomotive power for moving the blood through theextracorporeal flow path 100 is provided by a blood pump 302, which istypically located along the arterial 102 line. Blood is typicallyconveyed through the extracorporeal flow path 100 at a rate of 50 to 600mL/min and can be adjusted by a controller to any required rate suitablefor a procedure performed by the invention. Blood pump 302 can be aperistaltic pump, although those skilled in the art will readilyunderstand that other types of pumps can be used including diaphragmpumps, centrifugal pumps, and shuttle pumps. In certain embodiments, theblood pump 302 conveys blood through the dialyzer 701 where the blood iscontacted with a blood side of a dialysis membrane 702. Blood enters thedialyzer 701 through a blood inlet 504 and exits through a blood outlet505. The pressure of the blood prior to the blood pump 302 is measuredby a pressure sensor 602 and post dialyzer 701 by a pressure sensor 604.The pressure at pressure sensor 602 provides an indication of theadequacy of the blood flow in the arterial line connected to the bloodpump 302 inlet and a low or excessively negative pressure relative toatmosphere is an indication of a less adequate access flow that maycause the flow rate produced by blood pump 302 to be unacceptably belowthe set point flow rate. The pressure indication at pressure sensor 604can serve to detect obstructions in the venous bloodline and to monitortransmembrane pressure within dialyzer 701. An air trap 707 is placedalong the extracorporeal flow path 100 to prevent the introduction ofair into the circulatory system of the patient. The air trap 707 is notlimited to a particular design. Typical air traps can be drip chamberswith an air space that employ a hydrophobic membrane that allows air topass through the membrane while retaining water-based fluids.Alternatively the air trap 707 can be a chamber that is run full offluid and which traps any air at a point of greatest elevation andexchanges air via a hydrophobic membrane, such that there is no directair blood interface. Air-fluid detectors, or bubble detectors 601 and603 are present to confirm that air is not present in the extracorporealflow path 100. In some embodiments, air fluid detectors 601 and 603 canbe ultrasonic sensors that can detect a change in solution density orscattering due the presence of air or air bubbles.

Valve 402 controls flow into or out of the arterial line 102 ofextracorporeal flow path 100. Valve 401 controls flow into or out of thevenous line 105 of extracorporeal flow path 100. Valves 401 and 402 maybe pinch valves that control flow by non-invasively squeezing theexterior of the extracorporeal flow path to occlude the tubing toprevent flow. Occluding tubing in this manner refers to collapsing thetubing such that the inner lumen of the tubing is closed and flow isprevented from passing through collapsed portion. Other valves, such asdiaphragm valves that cause a moving or flexible member to block a floworifice can also serve this function.

Patient blood access sites are individualized; access types includecatheters, grafts and fistulas; and blood access procedures may varybetween patients. Any blood access type or method can be used and isnon-specific to the present invention. Line 104 indicates the arterialor supply portion of a patient's blood access and could be a fistulaneedle or catheter. Line 103 indicates the venous, or return portion ofthe patient's blood access and could be a fistula needle or catheter.

The patient's arterial blood access line 104 is connected to thearterial line 102 of the extracorporeal flow path 100 at connectionpoint 502. A non-limiting example of such a connector is a luerconnector. Similarly, the patient's venous blood access line 103 isconnected to the venous line 105 of extracorporeal flow path 100 atconnection point 501.

Drawing of blood samples and administration of therapeutic substancesvia the extracorporeal flow path 100 is contemplated by this invention.Any therapeutic substances that can be administered via the bloodthrough extracorporeal flow path 100 such as erythropoietin, iron, andvitamin D may be administered to the patient during dialysis therapythrough venous port 503. Further, blood samples may be withdrawn fromthe extracorporeal flow path 100 at arterial port 525 or venous port503. A non-limiting partial list of port designs may include cappedluer, petcocks, button membranes, and pre-split needle-free wherein oneof ordinary skill will understand that port designs in the art may beemployed without departing from the scope of the invention

During the course of conveyance of blood along the extracorporeal flowpath 100, heparin or other anticoagulant is added to the blood toprevent clotting of blood within the dialyzer 701 or blood conveyancepathway/extracorporeal flow path 100. Heparin or another anticoagulantis added from an anticoagulant container such as a syringe at a meteredrate using an anticoagulant pump 301. The anticoagulant pump 301 can beany pump capable of accurately metering the anticoagulant.

Water reservoir 202 holds a small volume of water that is used to createthe solution used for system priming, dialysis therapy, provision offluid bolus, blood rinse back and system cleaning and disinfection. Thewater reservoir 202 may be filled with potable tap water by the user.Alternatively, the water reservoir 202 may be filled with bottleddrinking water if potable water or other suitable types of water are notavailable. Purified water may also be used. Further, water reservoir 202may be the container of bottled drinking water itself. Other types ofwater suitable for use in dialysis systems including hemofiltration,hemodiafiltration and peritoneal dialysis are contemplated by thepresent invention. One of ordinary skill in the art will recognize thatit is possible to bypass water reservoir 202 and connect a potable watersource directly to port 510S as shown in FIG. 5C.

Degassing and De-Aeration of Water Supply

The water source used to supply water reservoir 202 may have significantamounts of dissolved gasses that could be released from solution insidethe controlled compliant flow path 110 to create air pockets thatdegrade performance of the system. Dissolved gasses may include thegaseous constituents of air such as nitrogen, oxygen and carbon dioxide.As detailed in FIG. 1C, the invention has a water degassing, orde-aeration circuit that can optionally be employed to remove dissolvedgasses from the water in reservoir 202 prior to mixing solution andpriming the fluid circuits. The arrows in FIG. 1C depict the directionof flow during the de-aeration process. During de-aeration, fluid intakebypass valve 404 is positioned to allow pump 305 to withdraw fluid fromwater reservoir 202 through intake line 113 and flow restriction 408 andheater 708. De-aeration of the water can be accomplished without havingheater 708 located in the de-aeration flow path and therefore heater 708and heating of the fluid can be considered optional to de-aeration. Pump304 is a positive displacement pump that is not operated during thisphase of operation and no flow passes through pump 304. De-aerationbypass valve 405 is positioned or set to direct flow from the outlet ofdialysate pump 305 through de-aeration bypass conduit 112 to line 114and back into water reservoir 202. Flow restriction 408 is sized suchthat when the dialysate pump 305 is operated at a predetermined rate,the pressure of fluid flowing through the restriction 408 drops to a lowabsolute pressure causing dissolved air to be released from solution andform gas bubbles. Non-limiting examples of flow restrictions areorifices, venturis, or narrow tubes. Heater 708 can optionally beoperated to increase the temperature of the fluid which further reducesthe solubility of air in water, enhancing the de-aeration process. Asthe fluid is recirculated in the de-aeration loop shown in FIG. 1C, airbubbles are released from solution and returned to water reservoir 202through lines 112 and 114, where they rise to the surface of the fluidin water reservoir 202 and are exhausted from water reservoir 202through vent opening 512. The de-aeration process recirculates the waterfor a predetermined time sufficient to de-aerate the water and,optionally, until no more bubbles are detected in the water flowing pastbubble detector 608.

Referring again to FIG. 1, dialysate within the system is conveyedthrough one of a first recirculating dialysate pathway or controlledcompliant flow path 110 which carries dialysate from outlet port 507 ofdialyzer 701 in a complete loop back to inlet port 506 of dialyzer 701,or a bypass flow path 111, which serves to bypass the dialyzer 701during certain system functions. The controlled compliant flow path 110can contain dialysate in certain embodiments, and be referred to as asolution conduit flow path. Bypass flow path 111 may be referred to as apriming or recirculation bypass in certain embodiments as describedfurther herein. The controlled compliant flow path 110 and bypass flowpath 111 have one or more conduits for conveying the dialysate. Flow iscontrolled to go through the controlled compliant flow path 110 orbypass flow path 111 by means of bypass valve 407. It is understood byone skilled in the art that three-way valve 407 can be replaced bytwo-way valves with the same result to control the flow through thedialyzer 701 or bypass flow path 111.

Dialysate that is conveyed through the dialyzer 701 on the dialysateside of the dialysis membrane 702 picks up waste products from theblood, including urea, by diffusion, ultrafiltration, hemofiltration orhemodiafiltration. Dialysate enters the dialyzer at a dialysate inletend 506 and exits at an outlet end 507. The dialysate exiting thedialyzer 701 passes through a blood leak detector 605 that can determinethe presence of blood in the dialysate indicating a breach in thedialysis membrane 702.

Valve 403 passes flow in only one direction such that fluid may notenter the dialyzer 701 through the outlet port 507, but may only enterthe dialyzer through inlet port 506, having first flowed throughmicrobial filter 706. In other embodiments, the valve 403 may be a 2-wayvalve under active control, or a 3-way valve under active controlallowing fluid back to the dialyzer 701 and positioned at junction 526.Microbial filter 706 removes residual bacteria and endotoxin from thedialysate, such that dialyzer membrane 702 becomes a redundant microbialbarrier between the dialysate and the blood. In other embodiments, themicrobial filter 706 can be placed in any portion of a flow path (notshown) to minimize system contamination. Suitable microbial filtersinclude commercially available hollow fiber ultrafilters having amembrane pore size sufficiently small to exclude passage of bothmicrobes and endotoxins and other such suitable filters known to thoseof ordinary skill in the art.

The dialysate is conveyed through heater 708 to heat the dialysate tothe prescribed dialysate temperature. Dialysate pump 305 provides thepumping action to cause the dialysate to flow through the controlledcompliant flow path 110, which can re-circulate dialysate. Flow ratesensor 609 measures dialysate flow rate for closed loop control ofdialysate pump 305 and/or measurement of dialysate flow rate to enablecontrol of infusate metering at a controlled ratio to the dialysateflow. In certain embodiments dialysate pump 305 can be a positivedisplacement metering pump and flow rate sensor 609 can be an optionalsensor. Pressure sensor 610 measures pressure of the dialysate beforeinlet port 513 of sorbent cartridge 703. The sorbent cartridge can be adisposable cartridge assembly that is disposed after use, a system ofindividual material containers, or a re-usable container that hascontents that can be opened and the contents replaced as needed.

Sorbent cartridge 703 removes waste products from the dialysate beforethe dialysate is re-conveyed through the dialyzer 701. The dialysateenters the sorbent cartridge 703 at a dialysate inlet end 513 and exitsat an outlet end 514.

In one non-limiting embodiment a static mixer 704 serves to ensure thatconcentrates added to the dialysate are thoroughly mixed before solutioncharacteristics such as conductivity are measured. In any embodiment, ifsufficient mixing of infusate and dialysate is obtained withoutemploying a static mixer, then the static mixer 704 may be considered tobe optional in that embodiment.

Degassing and De-Aeration During Priming

In certain embodiments, a degassing module 705 removes air during systempriming as well as gasses, such as carbon dioxide, introduced into thedialysate by the sorbent cartridge 703. Referring to FIG. 16, aschematic of a degassing module 705 is shown having an upper port 516that is a fluid inlet port, a lower port 519 that is a fluid outletport, a hydrophobic vent membrane 710 separating a flow through chamber220, and a space that is referred to as a gas collection chamber 221.Gas collection chamber 221 has a vent port 517 in communication with gasoutlet port 518, which is in communication with the atmosphere. Ventcontrol valve 410 can be operated to selectively permit gas to flowbetween gas collection chamber 221 and the atmosphere, and, when ventcontrol valve 410 is open, the pressure in gas collection chamber 221 isequal to atmospheric pressure. When vent control valve 410 is open,direction of gas flow depends upon the relative pressure differencebetween chambers 220 and atmosphere. If valve 410 is open and chamber220 has a pressure greater than atmospheric, any gas in chamber 220 thathas risen to contact hydrophobic vent membrane 710 will be forcedthrough hydrophobic vent membrane 710 and will be passed through gascollection chamber 221 and flow out to atmosphere through gas outletport 518. Conversely, if valve 410 is open and flow through chamber 220has a pressure less than atmospheric, air in contact with vent membrane710 will be forced through hydrophobic vent membrane 710 and will enterflow through chamber 220. During normal operation, the degassing modulecan be operated with a fluid pressure in flow through chamber 220 thatis greater than atmospheric to ensure that gas that has risen to contacthydrophobic vent membrane 710 will be exhausted from flow throughchamber 220. Degassing module 705 can be located in the controlledcompliant flow path 110 between pump 305 and dialyzer inlet port 506 asshown in embodiments depicted in FIGS. 1 and 1E, and between pump 305and replacement fluid port 538 on the venous line 105 of extracorporealcircuit 100, as shown the embodiment depicted in FIG. 1D. Otherpositions are possible in the present invention suitable for theintended purposes of degassing the system. The system can be normallyoperated with fluid pressures at ports 506 and 538 that are greater thanatmosphere and therefore the pressure inside degassing module 705 flowthrough chamber 220 will be greater than atmospheric also, thus causingany gas contacting hydrophobic vent membrane 710 to pass throughhydrophobic vent membrane 710 to atmosphere. Fluid pressure at pressuresensor 606 in the case of the embodiments depicted in FIGS. 1 and 1E, orfluid pressure at pressure sensor 604 in the embodiment depicted in FIG.1D can be monitored and, if the pressure drops to less than apredetermined amount greater than atmospheric, for example less than 25mm mercury above atmospheric, vent control valve 410 can be closed toprevent air ingress to degassing module 705. In certain embodiments, aflow restriction 409 is present in bypass flow path 111, as needed, toensure that sufficient back pressure remains in the main controlledcompliant flow path 110 to maintain adequate pressure inside thedegassing module 705 flow through chamber 220 relative to atmosphericpressure during operations where the dialysate flow is switched tobypass the dialyzer 701 through bypass flow path 111. Flow restriction409 may be an orifice, a venture, tubing with sufficiently small insidediameter to create the necessary restriction, an actuated restrictor,such as a pinch valve that compresses the tubing to constrict the flowpassing through bypass flow path 111, or any suitable element thatsufficiently restricts the fluid flow to maintain the desired fluidpressure upstream of the restriction.

The dialysate flow inlet 516 in FIG. 16 is placed at a higher elevationthan the dialysate outlet 519 so that the dialysate or fluid in thesystem flows in a downward direction through the module. It is a knownphenomenon that gas bubbles rise rates in aqueous solutions increase asthe diameter of the gas bubble increases wherein gas bubble rising ratesare known in the published literature. This principle can be applied toseparate the gas bubbles from the liquid to ensure that the bubbles donot pass out of flow through chamber 220 through fluid outlet port 519.The maximum fluid flow rate that will pass through the degassing module705 flow through chamber 220 can be determined wherein the crosssectional area of the chamber is selected such that the downward flowvelocity of the dialysate is less than the upward rise velocity of thesmallest bubble that the module is intended to capture.

In one embodiment, the degassing module has a flow-through chamber 220having a hydrophobic vent membrane 710 forming an upper portion of theflow chamber 220. The minimum elevation requirement for the location ofthe vent membrane is that it has an elevation greater than the fluidoutlet port 519. The hydrophobic vent membrane 710 has a sufficientpermeability and the surface area of hydrophobic vent membrane that isexposed to both chamber 220 and chamber 221 is sufficiently large toenable a flow of gas that is rising to the top of flow through chamber220 to contact hydrophobic vent membrane 710 will be caused to flowthrough hydrophobic vent membrane 710 to gas collection chamber 221 bythe pressure differential between the fluid in flow through chamber 220and the atmosphere. The hydrophobic vent membrane 710 is furtherrequired to have a sufficient water break through pressure, for examplegreater than 2 bar, so that liquid water does not pass from flow throughchamber 220 through hydrophobic vent membrane 710 to gas collectionchamber 221. Persons of skill in the art will be able to determine therange of operating pressures for flow through chamber 220 and a desiredrate of gas removal from flow through chamber 220 to determine acombination of membrane permeability and exposed membrane surface areathat is required for a particular application. An example of acommercially available membrane that can be suitable for a degassingmodule is Pall Corporation 0.2 micron pore size Emflon® part numberPTFE020LF0A.

Vent control valve 410 is opened to permit gas flow to atmosphere whenthe degassing module 705 is being operated to remove gas from thedialysate. Vent control valve 410 is closed to prevent air entry intothe controlled compliant flow path through the hydrophobic vent membraneduring certain operating functions of the system that may cause thedialysate pressure in the degassing module 705 to drop below atmosphericand undesirably pull air into the system. Vent control valve 410 isopened during other system functions where the dialysate pressure withindegassing module 705 is below atmospheric pressure and it is desirableto allow air to enter the controlled compliant flow path through thehydrophobic vent membrane at gas outlet port 518, for example when fluidis being drained from the controlled compliant flow path.

In FIG. 17, an embodiment of a degassing module 705 is shown that hasfluid inlet port 516 at a lower elevation in flow through chamber 220than fluid outlet port 519. The present design can be used if a flowcross section of the flow through chamber 220 is sufficiently largethat, at a maximum fluid flow rate for the degassing module, a fluidtransit time from fluid inlet port 516 to fluid outlet port 519 issufficiently long so that the smallest bubble that the degassing moduleis intended to capture will rise at least by the amount of an elevationdifference 150 and will rise above the elevation of fluid outlet port519 during the elapsed fluid transit time from fluid inlet port 516 tofluid outlet port 519.

FIG. 18 shows images from an embodiment of degassing module 705. Theleft hand view is an isometric view of the exterior of the degassingmodule. The right hand view is a section through a plane that passesthrough the axis of fluid inlet port 516 and the axis of fluid outletport 519. The embodiment has a body 715 that houses the flow throughchamber 220. The hydrophobic vent membrane 710 is shown in contact withthe cover 716. The surface of cover 716 that contacts hydrophobic ventmembrane 710 has a plurality of intersecting grooves that form gascollection chamber 221 and allow the gas to flow to vent port 517. Alsoshown is an o-ring seal 835 that serves to prevent fluid leakage fromthe seam between body 715 and cover 716. The methods of seal andattachment are exemplary and non-limiting, as those of skill in the artwill recognize that there are many methods to attach cover 716 to body715 and form a leak tight seal, for example adhesive bonding, ultrasonicbonding and overmolding. The shown o-ring seals 836 can provide fluidseals between fluid ports 516 and 519 and their mating ports of the basemodule. Again, the seal 836 and geometry of ports 516 and 519 areexemplary and non-limiting, as those of skill in the art will recognizethat there are many suitable seals, for example Q-rings, double seals,lip seals and face seals, and many fluid port geometries, for exampleluer connectors, Hansen connectors, and push to connect tube fittings.

Other types of degassing modules may be employed, such as parallel orwound hollow fiber assemblies. With these devices, a vacuum may beapplied to the gas side of the module to draw dissolved gas fromsolution in addition to removing gas bubbles. Non-limiting examples ofdissolved gasses include nitrogen, oxygen and carbon dioxide. If the gasbeing removed is carbon dioxide, the pH of the dialysate can beincreased without adding buffer, or by addition of less buffer.

Another type of degassing module that can be employed has a float thatcauses a seal to be pressed against an escape orifice when the chamberis full, or nearly full of liquid. When the chamber has trapped aquantity of gas sufficient to cause the liquid level to drop so that thefloat no longer presses the seal onto the orifice, gas is allowed toescape from the chamber. Microbial contamination of the fluid can beprevented by placing a microbial vent filter over the chamber outletopening to atmosphere.

In one non-limiting embodiment, the dialysate can flow through or acrossthe ammonia sensor 611 that detects a potentially hazardous conditionwhere the ammonia byproduct of urea breakdown escapes from sorbentcolumn 703. The ammonia sensor may use optical methods to detect a colorchange of ammonia and/or ammonium sensitive media contained withinsensor 611. If ammonia and/or ammonium are detected, control actionswitches bypass valve 407 to direct dialysate flow to bypass flow path111 and prevent out of tolerance dialysate from passing through thedialyzer 701. Further, one-way valve 403 prevents the ammonia and/orammonium bearing dialysate from backing up into the dialyzer 701. Assuch, the dialysate can be circulated through the sorbent cartridge 703while bypassing the dialyzer 701 and preventing contact with thepatient's blood when required.

Temperature sensor 612 measures the temperature of the dialysate toverify that it is within the predetermined temperature limits beforepassing through dialyzer 701. If the temperature is out of tolerance,control action switches bypass valve 407 to direct dialysate flow tobypass flow path 111 and prevent out of tolerance dialysate from passingthrough the dialyzer 701 and further recirculated until the dialysatetemperature is within acceptable limits. Temperature sensor 612 may alsobe used for closed loop control of dialysate temperature by action ofthe controller and heater. Refreshed dialysate exiting an outlet end ofthe sorbent cartridge 703 can be monitored by a conductivity sensor 613.The design of any conductivity sensor employed in embodiments describedherein is not particularly limited; however, a typical conductivitysensor has two electrodes where a current between the two electrodes ismonitored. The presence of sodium ions in the dialysate is the majorcontributor to the conductivity measured by conductivity sensor 613.Conductivity is continually monitored and reported to the controller toassess the quality and safety of the dialysate. When the conductivity ofthe dialysate falls within a predetermined range, the dialysate isdirected by valve 407 to a dialysate inlet end 506 of the dialyzer 701;the valve 407 is located between an outlet end 514 of the sorbentcartridge 703 and the dialysate inlet end 506 of the dialyzer 701. Incertain embodiments, the valve 407 is a three-way valve. The controlaction of valve 407 can also be accomplished by a pair of 2-way valves.

When the conductivity measured by conductivity sensor 613 is outside ofthe predetermined range, the valve 407 can direct the dialysate to beconveyed through the bypass flow path 111 and bypass the dialyzer 701.Further, one-way valve 403 prevents the dialysate from backing up intothe dialyzer 701. As such, the dialysate can be circulated through thesorbent cartridge 703 while bypassing the dialyzer 701 and preventingcontact with the patient's blood until the sodium has been adjusted bycontrol action of the system. The system reduces sodium concentrationwithin the controlled volume dialysate circuit by simultaneouslyoperating water pump 304 to add water from water reservoir 202 whilesimultaneously operating fluid balance control pump 303 to remove anequal volume of dialysate by pumping it to solutions reservoir 201. Ifconductivity is low, the system can increase sodium concentration byswitching salination valve 406 to direct flow through a sodium conduitflow path in fluid communication with sodium chloride cartridge 203 andpump saturated sodium solution into the dialysate by pumping andmetering action of salination pump 307.

The dialysate is filtered through a microbial filter 706 before passinginto dialyzer 701 through inlet 506. Sorbent cartridge 703 performs ahigh degree of bacterial and endotoxin removal from the solution and themicrobial filter 706 further removes residual bacteria and endotoxinsuch that the resulting solution is capable of meeting the microbialpurity standard for ultrapure dialysate and dialyzer membrane 702becomes a redundant barrier to passage of bacteria from the dialysatecompartment to the blood compartment by solution that is transferredacross dialysis membrane 702.

Typically, the output of the sorbent cartridge in prior art sorbentsystems meets the Association for the Advancement of MedicalInstrumentation's (AAMI) Water for Hemodialysis standard but does notmeet the AAMI standard for microbiologically ultrapure dialysate. It hasbeen shown in the medical literature that ultrapure dialysate isdesirable in reducing the inflammatory response in the ESRD patient.Desirable quality for ultrapure dialysate is less than about 0.1 colonyforming unit (cfu)/mL where cfu is the number of viable cells per unitvolume, and detectable endotoxins less than about 0.03 endotoxin unit(EU/mL). Suitable filters include ultrafilters and micro filtersmanufactured or supplied by Medica, however any known by those ofordinary skill for the intended purpose can be used.

The pressure of the dialysate entering the dialysate inlet end of thedialyzer 701 can be measured by a pressure sensor 606.

The components forming the controlled compliant flow path 110 can have acontrolled compliant volume wherein the controlled compliant flow path110 further incorporates a control pump such as fluid balance controlpump 303 that can be operated bi-directionally to cause the net movementof fluid from an extracorporeal side of the dialyzer 701 into thecontrolled compliant flow path 110 or to cause net movement of fluidfrom the controlled compliant flow path 110 into the extracorporeal sideof the dialyzer 701. In particular, the control pump 303 or any suchsimilar pump can be operated in the efflux direction to cause themovement of fluid from the extracorporeal side of the dialyzer 701 intothe controlled compliant flow path 110 and in the influx direction tocause the movement of fluid from the controlled compliant flow path 110into the extracorporeal side of the dialyzer 701. In this manner, thenet volume of fluid crossing the dialysate membrane 702 between thedialysate compartment and the blood compartment can be under directcontrol and can be accurately determined.

In certain embodiments, operation of the control pump 303 in the influxdirection to drive liquid into the controlled compliant flow path 110and subsequently cause movement of fluid from the controlled compliantflow path 110 to the extracorporeal side of the dialyzer 701. Thecontrol pump 303 can also be used for the movement of fluid in theopposite direction across the dialyzer 701 into the controlled compliantflow path 110. It is noted that the solution reservoir 201 or any othersuitable reservoir attached to the controlled compliant flow path 110can allow the system to adjust the patient fluid volume by withdrawingfluid and storing the desired amount in the respective reservoir and/orby providing rebalanced fluids to the patient and removing wasteproducts. For example, the fluid stored in a solution reservoir 201attached to the controlled compliant flow path can be used to store avolume of fluid equal to the ultrafiltrate volume removed from thepatient during ultrafiltration (UF). Alternatively, the fluid stored inany fluid reservoir attached to the controlled compliant flow path 110can contain a desired infusate. In certain embodiments, the deliveredfluid can contain a therapeutic component deliverable across thedialyzer 701 and into the patient's bloodstream. Additionally, thevolume of the controlled compliant flow path 110 can be activelycontrolled by the user or a programmed controller.

In certain embodiments, the control pump 303 can allow for fluid to movefrom the controlled compliant flow path 110 to the extracorporeal sidewithout creating a vacuum, wherein the operation of the control pump 303is controlled as described herein. Likewise, the control pump 303 canallow for fluid to move from the extracorporeal side, and hence thepatient's body via the action of the pumps. The net movement of fluidbetween the extracorporeal side of the dialyzer 701 and the controlledcompliant flow path 110 can be accurately controlled and metered usingthe removed fluid in certain embodiments. In other embodiments, theremoved fluid can be transferred back to the patient through controlledcompliant flow path 110 using the solution stored in solution reservoir201. In some embodiments, the solution reservoir 201 can be prefilledwith water, dialysate or other fluid for addition to the controlledcompliant flow path 110.

As such, embodiments of the invention can have a controlled compliancecontrolled compliant flow path 110 that is accurately controlled toprecisely remove or add fluid to the extracorporeal side of the dialyzer701. Due to the substantially inflexible void volume of the componentsand connecting conduits of the controlled compliant flow path 110, netmovement of fluid or water is prevented from moving in either directionacross the membrane 702 between the extracorporeal flow path 100 of thedialyzer 701 and the controlled compliant flow path 110 of the dialyzer701. Specifically, due to the controlled compliance feature of the voidvolume of the controlled compliant flow path 110, water cannot passivelymove in either direction between the extracorporeal side and thedialysate side through the dialysis membrane 702. In the event offactors that tend to increase pressure on the extracorporeal side of thedialysis membrane, such as increased blood flow rate or blood viscosity,pressure across the membrane will automatically be equalized due to thelimited volume of the controlled compliant flow path 110 and thenon-compressible nature of the dialysate. In the event of factors thattend to increase pressure on the dialysate side of the dialysis membrane702, such as increased dialysate flow rate, net movement of water fromthe controlled compliant flow path 110 to the extracorporeal flow path100 is prevented by a vacuum that would form in the controlled compliantflow path 110 in the event of such a movement. This capability canfurther be used to enhance the convective clearance of the system foruremic impurities while controlling the net fluid removed from thepatient, for example, creating periods of fluid movement across themembrane with occasional reversal of direction. In certain embodiments,an ultrafiltrate can be used as described herein. However, the presentinvention is not limited to a controlled compliance flow path whereinthe controlled compliant flow path 110 in certain embodiments is not acontrolled compliance flow path and may include one or more openreservoirs for storing or accumulating dialysate.

Since the dialyzer can be a high-flux type there is some fluid flux backand forth across the dialyzer membrane due to the pressure differentialon the blood and dialysate sides of the membrane. This is a localizedphenomenon due to the low pressure required to move solution across themembrane and is called back-filtration, however results in no net fluidgain or loss by the patient.

The fixed volume controlled compliant flow path, as described, enablesthe fluid balance control pump 303 to be operated in concert with thewater pump 304 and acid concentrate pump 306 such that net fluid removalor subtraction from the controlled compliant flow path 110, and thus theextracorporeal flow path 100 can be precisely determined and controlledaccording to a simple volumetric control algorithm that is expressed byas sum of the volumes in following formula.Patient Fluid Balance+Fluid Balance Control Pump+Water Pump+Acid Conc.Pump+Σ_(i+0) ^(n) X _(i)=0The term “Patient Fluid Balance” refers to the volume of fluid added toor removed from the patient by net movement of fluid across the dialyzermembrane 702. The algebraic sign of each term of the above formula isdetermined by whether the flow is efflux or influx to the controlledcompliant flow path 110. The term X refers to the volumetric flow rateof a pump where the number of pumps can range for n from 0 to 20. Theterm “n from 0 to 20” means any integer value of 0, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. The formula appliesto an instantaneous rate of fluid removal. The instantaneous net fluidremoval rate can also be integrated over the time course of therapy todetermine the net fluid removal during the elapsed therapy time. Thus,the system can operate the aforementioned pumps to selectively meter inand meter out fluid from the flow loop to accomplish a predeterminedpatient fluid balance at any time throughout the course of a therapydelivery session.

In certain embodiments, any one of the control pumps of the inventioncan be a peristaltic pump, a volumetric metering pump, diaphragm pump,or a syringe style pump. Hence, the controlled compliant flow path 110has a substantially inflexible volume that can deliver controlledchanges in volume modulated by the control pump 303 and optionally anyother pump(s) that add or remove fluid to and from the controlledcompliant flow path 110. The contents of U.S. patent application Ser.No. 13/565,733 filed on Aug. 2, 2012 are incorporated herein byreferences in their totality.

In certain embodiments, the controlled compliant flow path 110 can havea total void volume from about 0.15 L to about 0.5 L. In otherembodiments, the controlled compliant flow path 110 can have a voidvolume from about 0.2 L to about 0.4 L or from 0.2 L to about 0.35 L.Other volumes can be envisioned by those of ordinary skill in the artdepending on parameters such as patient weight, size, and healthcondition. The system can be designed to be a portable system, a desktopsystem or a large system suitable for heavy use in a clinical setting.Hence, both large volumes greater than 0.5 L to about 5 L, andmicro-volumes from as small as 0.1 L to about 0.5 L such as 0.1 L to 0.2L, 0.1 L to 0.3 L, 0.1 L to 0.4 L, 0.2 L to 0.3 L, 0.3 L to 0.4 L, or0.3 L, 0.5 L, or greater volumes of about 1 L, 2 L, 3 L, 4 L, or 5 L arecontemplated by the invention.

Infusates such as sodium chloride and sodium bicarbonate which haveaqueous solubility limits greater than their concentration in dialysatecan be produced on line by reconstituting a saturated solution from acontainer having a mass of solute greater than the amount of soluterequired for a therapy session, such that a reserve of solute persistsand the solution in the container remains saturated. Although solubilitydoes vary with temperature, the circulating dialysate temperature iscontrolled by heater 708 and the temperate of the solution exiting thecontainers may be optionally measured by temperature sensor 614 locatednear the outlet of the containers such that actual concentration ofinfusate can be determined from empirical temperature-solubility curves.

Salination valve 406 directs the saturated solution flow path througheither sodium chloride cartridge 203 having an excess of the solutesodium chloride, or through a buffer conduit flow path in fluidcommunication with sodium bicarbonate cartridge 204 having an excess ofthe solute sodium bicarbonate. The excess amount of solute can be anamount of solute greater than a predetermined amount of the solute thatmay be consumed during the course of normal operation of the system,such that some undissolved solute remains in the cartridge or container.The excess undissolved solute can result in solution exiting thecartridge or container that can be maintained in an essentiallysaturated state by virtue of the excess solute that remains available todissolve into solution. It is readily apparent to one skilled in the artthat the function of 3-way valve 406 could be replaced by two 2-wayvalves to accomplish the same fluid circuit functionality. Other valvearrangements whether 2-way, 3-way or more having differentconfigurations to achieve the same effect is contemplated by the presentinvention.

In a preferred embodiment, sodium chloride cartridge 203 and bicarbonatecartridge 204 are supplied in dry form and then hydrated to produce asaturated aqueous solution during the water intake and priming steps ofsystem operation. This eliminates microbial growth that is possible withbicarbonate that is supplied as an aqueous solution and also reduces thetransportation weight of the supplies. In FIG. 19, a fluid flow throughbicarbonate cartridge 204 can reconstitute a saturated aqueous solutionfrom a dry sodium bicarbonate as shown. Fluid can enter through port524, pass through a first proximal layer of filter material 711, throughflow through chamber 222, then pass through a second distal layer offilter material 711, and then out through fluid outlet port 523. Thefunction of the filter material 711 can be to retain the sodiumbicarbonate inside chamber 222 during storage and transport and also toprevent undissolved sodium bicarbonate particles from passing out ofchamber 222 when fluid is flowing through chamber 222. Blown or spundepth filter media are preferred for filter material 711. An amount ofdry sodium bicarbonate that is greater than the amount that will beconsumed during operation of the system is contained in flow throughchamber 222. The fluid flowing through chamber 222 can dissolve thesodium bicarbonate until a saturated solution is produced. The fluidpassing out of bicarbonate cartridge 204 at fluid outlet port 523 canremain saturated as long as an amount of undissolved sodium bicarbonateremains in flow through chamber 222. Saturation concentration of sodiumbicarbonate is well known, including its variation with temperature.Temperature sensor 614 can measure the temperature of the solutionexiting through fluid outlet port 523 to enable a controller todetermine the sodium bicarbonate concentration of the fluid exiting thebicarbonate cartridge 204. It should be further noted that the solutionthat is metered from flow path 100 through the bicarbonate cartridge 204by action of pump 307 can contain other solutes, principally sodium andchloride, that these solutes affect the saturation concentration ofbicarbonate in bicarbonate cartridge 204, and the effect of thesesolutes, whose concentrations are also controlled by the system, can betaken into account when determining the bicarbonate concentration in thesaturated bicarbonate cartridge 204. The rate of salination pump 307 canbe adjusted accordingly by a controller to maintain the desired rate ofsodium bicarbonate infusion from conditioning conduit flow path 115 tothe controlled compliant flow path 110 and filtrate regeneration circuit120.

In FIG. 20 an embodiment of a bicarbonate cartridge 204 is shown. Fluidcan enter through fluid inlet port 524, and can pass through a firstproximal filter layer 711, then through flow through chamber 222containing an amount of sodium bicarbonate in excess of the amount thatwill be consumed by operation of the system, through a second distalfilter layer 711, and then exits through fluid outlet port 523. Theenclosure of the bicarbonate cartridge is formed by base 717 and cover718. In the embodiment shown, there can be a lap joint positionedbetween base 717 and cover 718. The lap joint configuration is anon-limiting example of an embodiment of the invention wherein those ofskill in the art will recognize that many suitable methods of attachmentand sealing of the cover 718 to body 717, for example adhesive bonding,snaps with elastomeric seals, threads, spin welding, ultrasonic weldingand press fitting are available. Also shown are o-ring seals 836 thatprovide fluid seals between fluid ports 524 and 523 and their matingports of the base module. The seals 835 and the geometry of ports 524and 523 are exemplary and non-limiting, as those of skill in the artwill recognize that there are many suitable seals, for example Q-rings,double seals, lip seals and face seals, and many fluid port geometries,for example luer connectors, Hansen connectors, and push to connect tubefittings, any of which can be used in the present invention.

As shown in FIG. 1, the dialysate is recirculated through the controlledcompliant flow path 110 by a dialysate pump 305. When the fluid balancecontrol pump 303, water pump 304, salination pump 307, and acidconcentrate pump 306 are not operating, fluid along the length of thecontrolled compliant flow path 110 flows into and out of the dialyzer701 at a rate determined solely by the action of the dialysate pump 305.In some embodiments, the dialysate pump can be operated at a rate fromabout 50 to about 800 mL/min. The dialysate pump 305 can be a positivedisplacement pump such as a reciprocating metering pump, a diaphragmpump, or peristaltic roller pump. The dialysate pump 305 selection isnot limited to positive displacement pumps and may be a gear pump, vanepump, or centrifugal pump. In one embodiment, a gear pump can be used inthe controlled compliant flow path 110. In the extracorporeal path 100,a peristaltic pump can be used. However, it will be understood that manyother types of pumps known to those of skill in the art can be used.

In preferred embodiments, fluid balance control pump 303 can operatebi-directionally to meter fluid between solution reservoir 201 and thecontrolled compliant flow path 110 and the fluid balance control pump303 is a positive displacement pump. Non-limiting examples of positivedisplacement pumps include fixed volume, reciprocating piston pumps,diaphragm pumps or peristaltic roller pumps.

Water pump 304 is normally operated in an influx direction to meterwater from water reservoir 202 into the controlled compliant flow path110. Water pump 304 is a positive displacement pump. Non-limitingexamples of positive displacement pumps include fixed volume,reciprocating piston pumps, diaphragm pumps or peristaltic roller pumps.

Salination pump 307 is operated to meter fluid from the controlledcompliant flow path 110 through cartridges within a conditioning flowpath 115 containing an amount of solute greater than the aqueoussolubility of the solute such that saturated solutions of an infusatesuch as sodium chloride or sodium bicarbonate are metered back into thecontrolled compliant flow path 110 to enable the concentration of one ormore solutes in the dialysate to be increased in the dialysate.Salination pump 307 is a positive displacement pump. Non-limitingexamples of positive displacement pumps include fixed volume,reciprocating piston pumps, diaphragm pumps or peristaltic roller pumps.

In FIG. 1, the salination pump 307 can pull dialysate after the outletof the sorbent cartridge 703 and returns the fluid to the controlledcompliant flow path 110 at a point upstream of the dialysate pump inlet.The configuration shown in FIG. 1 is one non-limiting example where oneof ordinary skill can envision other points on the controlled compliantflow path 110 for returning fluid either pre, or post sorbent cartridge703. Specifically, and with reference to FIG. 1, the function ofsalination pump 307 is to meter a controlled volume of fluid from thecontrolled compliant flow path 110 through a conditioning flow path 115containing a saturated solution cartridge and return to the controlledcompliant flow path 110 an equal volume of saturated solution. The fluidcan be returned to the controlled compliant flow path 110 at a range ofpoints between bypass junction 526 and conductivity sensor 613.Referencing FIG. 1C, it is further noted that the salination pump 307can intake fluid at a range of points from bypass junction 526 andconductivity sensor 613, with the preference that the inlet to pump 307is located at a point on the controlled compliant flow path 110 that isnot immediately downstream from the outflow of concentrated solutionpassing from valve 406 back to the controlled compliant flow path 110.

Electrolyte concentrate, or acid concentrate pump 306 is normallyoperated in an influx direction to meter a concentrate containingelectrolytes such as K⁺, Mg⁺⁺, Ca⁺⁺ and other substances constitutingthe dialysate prescription from the acid concentrate reservoir 205. Acidconcentrate pump 306 is a positive displacement pump. Non-limitingexamples of positive displacement pumps include fixed volume,reciprocating piston pumps, diaphragm pumps or peristaltic roller pumps.

Due to the substantially inflexible void volume of the circuitcomponents and connecting conduits that constitute the controlledcompliant flow path 110, the net movement of fluid over any timeinterval across the dialysis membrane 702 can be accurately controlledby precisely removing or adding fluid volume to the controlled compliantflow path by coordinated action of one or more of the pumps 303, 304 and306. Thus a means to accurately introduce or remove fluid from thepatient is provided.

FIG. 1D shows an embodiment employing a hemofiltration approach. Thecomponents shown in FIG. 1D are comparable to FIG. 1 where the samereference numbers refer to like elements. During hemofiltration,filtrate from the blood is drawn across membrane 732 through filtratepump 335 and waste species are removed from the blood by the action ofsolvent drag as the filtrate passes through membrane 732. The pumpingrate of filtrate pump 335 determines the rate of convective filtration.As such, a dialysate is not circulated through hemofilter 731. Rather, afiltrate fluid is removed from blood at hemofilter 731 and a replacementfluid is regenerated for reintroduction to the patient via the venousline 105 at port 538 to prevent hypovolemia that would occur due toexcessive fluid removal in the absence of replacement fluid return.

The components and conduits that comprise a filtrate regenerationcircuit 120 and bypass flow path 111 are substantially inflexible suchthat a controlled compliance filtrate regeneration circuit is createdand, as described for FIG. 1, pumps 303, 304 and 306 can be operated toprecisely control net fluid removal or addition to a subject receivingtherapy. As such, the fluid balance control pump 303 can be operated inconcert with the water pump 304 and acid concentrate pump 306 such thatnet fluid removal or subtraction from the filtrate regeneration circuit120, and thus the extracorporeal flow path 100 can be preciselydetermined and controlled according to a simple volumetric controlalgorithm that is expressed by as sum of the volumes in given in thefollowing formula. Filtrate regeneration circuit 120 can also bereferred to as a solution conduit flow path.Patient Fluid Balance+Fluid Balance Control Pump+Water Pump+Acid Conc.Pump+Σ_(i+0) ^(n) X _(i)=0

“Patient Fluid Balance” refers to the volume of fluid added to orremoved from the patient by net movement of fluid removed as filtratethrough hemofilter membrane 732 and returned as replacement fluidthrough port 538 of the extracorporeal flow path 100. The algebraic signof each term of the above formula is determined by whether the flow isefflux or influx to the filtrate regeneration circuit 120. The term Xrefers to the volumetric flow rate of a pump where the number of pumpscan range for n from 0 to 20. The term “n from 0 to 20” means anyinteger value of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, or 20. The formula applies to an instantaneous rate offluid removal. The instantaneous net fluid removal rate can also beintegrated over the time course of therapy to determine the net fluidremoval during the elapsed therapy time. Thus, the system can operatethe aforementioned pumps to selectively meter in and meter out fluidfrom the flow loop to accomplish a predetermined patient fluid balanceat any time throughout the course of a therapy delivery session.

In some embodiments, the amount of replacement fluid returned to thesubject is substantially the same as the volume removed through thehemofilter 731. In other embodiments, the volume of replacement fluidinfused into the subject is less than the volume removed through thehemofilter 731 to affect a net fluid removal from the subject.

Filtrate can be removed from the hemofilter 731 through outlet 537 andthe pressure of the removed fluid (i.e. filtrate fluid) is monitored bypressure sensor 615. Blood leak detector 605 monitors the filtrate forpresence of blood in the filtrate that would indicate a breach ofhemofilter membrane 732. FIG. 1 describes the use of system componentsto modify the composition of a dialysate to maintain physiologicalcompatibility. Similar system components can be used to modify thecomposition of the regenerated filtrate to produce a replacement fluidfor reinfusion to the venous line 105 via port 538.

Prior to the initiation of hemofiltration treatment, the conduits of thesystem must be primed with a physiologically compatible solution. Asdescribed for FIG. 1, water from reservoir 202 is optionally de-aeratedand then drawn into filtrate regeneration circuit 120 by action of pump304. As described, sodium cartridge 203 and bicarbonate cartridge 204,in conjunction with salination valve 406 and pump 307, can be used togenerate an predetermined level of sodium ion and buffer to generate aphysiologically compatible priming solution. The solution produced canthen be circulated through bypass flow path 111, which functions as apriming and recirculation loop, by action of valve 407. In general, thesteps for controlling generation the physiologically compatible solutionare as follows: (1) H2O pump=Control Pump; (2) Salination pumprate=((solution target/NaCl conc.))×H2O pump rate)+((deltaconductivity/NaCl conc.)×solution conduit flow rate).

As described for FIG. 1, the physiological priming solution is movedinto the therapy solution reservoir 201 by action of control pump 303and the process continues until a predetermined amount ofphysiologically compatible solution sufficient for priming, fluid bolus,and blood rinse-back has been produced and reserved in reservoir 201.

Once the predetermined volume of physiologically compatible solution hasbeen produced and moved to the therapy solution reservoir 201, pump 303can be reversed to begin moving a portion of the prepared solutionvolume contained in reservoir 201 back to the filtrate circuit and valve407 is now positioned to allow the solution volume to pass throughmicrobial filters 706 and 709 and into the extracorporeal flow path atport 538. Priming of the extracorporeal flow path continues as describedfor FIG. 1, except that the physiologically compatible priming solutionenters the extracorporeal circuit at port 538 instead of across dialyzer701 membrane 702, and air in the extracorporeal flow path is moved to ahydrophobic vent 560 located at the terminal ends of extracorporeal flowpath 100 as shown in FIG. 4B or into priming over flow reservoir 210 asshown in the examples of FIG. 4A and FIG. 4C. Additionally, as theextracorporeal flow path fills with the priming solution, fluid passesacross the hemofilter membrane 732, exiting hemofilter 731 through port537, returning to the filtrate regeneration circuit 120. Any air passedinto filtrate regeneration circuit 120 with the fluid exiting hemofilter731 at port 537 is exhausted by action of degassing module 705 locatedin filtrate regeneration circuit 120 before the solution is circulatedback to the extracorporeal flow path. During this process, infusates canbe added from concentrate reservoir 205 by action of pump 306 to addadditional cations and components (e.g. potassium ions, magnesium ions,calcium ions, etc.) to the solution.

Upon initiation of hemofiltration treatment, waste species are removedfrom the filtration fluid by sorbent cartridge 703. Infusates can beadded from concentrate reservoir 205 by action of pump 306 to addnecessary cations and components (e.g. potassium ions, magnesium ions,calcium ions, etc.) to regenerate a replacement fluid solution. Thetreated filtrate is then passed through the degas module 705, microbialfilters 706 and 709 to complete preparation of the replacement fluidsolution prior to its introduction to the venous line 105 at port 538for infusion into the patient. The replacement fluid solution may benecessary for preventing hypovolemia, and can replace at least a portionof the fluid volume removed as filtrate from the blood of the subject.Replacement fluid can also be referred to as a substitution fluidwherein such terms are used interchangeably in the present invention. Asin FIG. 1, ammonia sensor 611, temperature sensor 612, and conductivitysensor 613 monitor the replacement fluid to verify that it remainswithin predetermined limits. If the solution composition is outside ofpredetermined limits, valve 407 diverts the solution through bypass flowpath 111, functioning as a priming and recirculation loop, until thefluid has been corrected. Those skilled in the art will understand thatthe composition of the filtrate (e.g. sodium ion concentration,conductivity) may not always match a desired composition for areplacement fluid. As such, the sodium cartridge 203 and the bicarbonatecartridge 204 can be used to modify the composition of the filtrate asnecessary to allow a suitable replacement fluid to be generated. Forexample, conductivity of the filtrate fluid can be increased using theconditioning pathway 115 by operating pump 307 and valve 406. Similarly,conductivity can be lowered through addition of water from reservoir 202by action of pump 304 and excess fluid can be removed through operationof pump 303. A additional pressure sensors can be added in thereplacement fluid pathway before microbial filter 706 and betweenmicrobial filters 706 and 709 to monitor condition of the filtersindependently. As described for FIG. 1, a fluid bolus can be provided tothe subject by delivering additional solution volume from reservoir 201to the filtrate regeneration circuit 120 via action of pump 303, exceptthat the bolus fluid volume enters the extracorporeal circuit at port538 instead of passing across dialyzer 701 membrane 702.

FIG. 1E shows an embodiment to perform hemodiafiltration therapy. Thissystem is the same as the hemodialysis system shown in FIG. 1, exceptthat a replacement fluid metering pump 308 and a redundant microbialfilter 709 have been added to the circuit wherein effluent dialysateexits the dialyzer 701 via outlet 507 and returns via inlet 506. Thereplacement fluid metering pump 308 may be a reciprocating type pistonpump, or a diaphragm pump, or a peristaltic pump. Microbial filter 709may be an individual microbial filter, or multiple redundant microbialfilters in series. Because the controlled compliant flow path 110, alsoreferred to as a solution conduit flow path, has a controlled compliantvolume, operation of replacement fluid metering pump 308 causesadditional filtrate to be pulled from the blood across membrane 702 intothe dialysate compartment for enhanced clearance by convection acrossthe dialysis membrane. This filtrate is combined into the effluentstream passing through dialyzer outlet 507 returning to the sorbentcartridge 703 where impurities are removed. The combined dialysate andfiltrate stream is then reinfused with cations from concentratereservoir 205 and continues toward the dialyzer inlet 506. Prior toreaching dialyzer inlet 506, replacement fluid metering pump 308redirects a portion of the regenerated fluid through microbial filter709 as replacement fluid solution into the venous line 105 of theextracorporeal flow path at port 538.

Because of the controlled compliance of the controlled compliant flowpath 110, net fluid removal from the subject can be determined bycalculating the algebraic sum of the flow rates of control pump 303,water pump 304, electrolyte pump 306 and replacement fluid metering pump308 per unit time according to the following formula.Patient Fluid Balance+Fluid Balance Control Pump+Water Pump+Acid Conc.Pump+Replacement Fluid Pump+Σ_(i=0) ^(n) X _(i)=0

The term “Patient Fluid Balance” refers to the volume of fluid added toor removed from the patient by net movement of fluid across the dialyzermembrane 702 and into the extracorporeal flow path 105 at port 538. Thealgebraic sign of each term of the above formula is determined bywhether the flow is efflux or influx to the controlled compliant flowpath 110. The formula applies to an instantaneous rate of fluid removal.The instantaneous net fluid removal rate can also be integrated over thetime course of therapy to determine the net fluid removal during theelapsed therapy time. The term X denotes the volumetric flow rates ofother possible pumps where n can range from 0 to 20. It will beunderstood that many possible permutations of numbers and types of pumpsand reservoirs can be used together in the above described formulawithout departing from the scope of the invention.

Each of control pump 303, water pump 304, acid concentrate pump 306 andreplacement fluid metering pump 308 can be operated under coordinatedactive control where volumetric pumping rates can be independentlyadjusted and one or more can be turned on or off as required to achievea prescribed fluid composition and a prescribed fluid removal from thesubject undergoing therapy.

FIG. 2 shows an embodiment in which base module 803 is in fluidcommunication with the controlled compliant flow path components of anoptional therapy cassette 820. Therapy cassette 820 can containconsumable and disposable items required for therapy and can bedetachably mounted on the base module 803. Therapy cassette 820 cancontain a dialyzer 701, one or more infusates 804 and one or moresolution reservoir 201. The infusates can be in the form of drymaterials or solutions. In some embodiments, the therapy cassette 820can contain a dialyzer and one or more infusate reservoirs wherein thedialyzer or infusate containers 804 may or may not be fully detachablefrom the therapy cassette (not shown). In other embodiments, the therapycassette can contain the dialyzer and one or more solutions reservoir201 wherein either may or may not be fully detachable from the therapycassette (not shown). During therapy, the blood circulation of subject850 is in fluid communication with dialyzer 701 contained in therapycassette 820. In certain embodiments, connected water reservoir 202 canbe detachably connected to the system or formed integrally with one moresystem components such as the base module 803. During operation, thewater reservoir 202 is in fluid communication with the base module.Sorbent cartridge 703 is also in fluid communication with the basemodule 803. The actions of the base module are controlled by controller802. Control module 802 sends messages to and receives commands from theuser through user interface 801. Whether combined into the optionaltherapy cassette 820, or individually mounted on base module 803, in anyembodiment the dialyzer 701, infusates 804, solution reservoir 201,sorbent cartridge 703 and water reservoir 202 are in fluid communicationwith the jumpered ports (not shown) of base module 803 to complete acontrolled compliant dialysis flow path for purposes of deliveringtherapy to a subject.

FIG. 3 shows the re-usable fluid path components and ports of thecontrolled compliant flow path 110 of FIG. 1 contained within basemodule 803 of FIG. 2. Dotted lines added to the fluid circuit diagramindicate fluid path connections that are established by jumper pathways860-871 contained within a cleaning manifold 840 shown in FIG. 6A. Thejumpers contained in cleaning manifold 840 complete the fluid circuitsegments that were opened by removal of the disposable and consumablecomponents upon therapy completion prior to the cleaning and/ordisinfection process. The jumpers create completed fluid circuits toenable fluid to be flushed and recirculated through the re-usablecomponents contained in base module 803 for purposes of cleaning and/ordisinfection. The dotted lines shown in FIG. 3 provide a single,non-limiting example of a configuration to jumper the fluid ports.Alternative jumpered port combinations are contemplated by thisinvention and those skilled in the art will recognize that othercombinations of jumpered ports can be employed to create completed fluidcircuit pathways for purposes of flushing fluids and recirculation of acleaning and/or disinfection fluid throughout the re-usable portions ofthe controlled compliance dialysate fluid circuit.

A cleaning manifold 840 having the fluid circuit jumpers and ports ofFIG. 3 is shown in FIG. 6A. The circuit jumpers, or fluid port jumpers,connect to the fluid ports of the base module 803 to complete the fluidcircuit where the disposable and consumable components of the controlledcompliance controlled compliant flow path have been removed uponcompletion of therapy. When cleaning manifold 840 is installed on basemodule 803, the cleaning manifold fluid ports 506M, 507M, 508M, 509AM,510AM, 515M, 516M, 519M, 522M, 523M, 524M, 530M, and 531M shown in FIG.6A engage the corresponding fluid ports 506S, 507S, 508S, 509S, 510S,515S, 516S, 517S, 519S, 522S, 523S, 524S, 530S, and 531S of base module803 shown in FIG. 5C. FIG. 6A also shows fluid ports 509BM and 510BMthat connect to lines 113 and 114 of FIG. 3, respectively, to enablefluid communication between cleaning manifold 840 and reservoir 202. Oneof ordinary skill in the art will recognize that water reservoir 202 canbe bypassed by connecting a suitable water source directly to fluid port510BM of cleaning manifold 840 if the water source will not requiredeaeration by the system before use in the cleaning and/or disinfectionprocess.

During cleaning and disinfection a volume of water may be firstde-aerated as necessary by the method described earlier. Duringde-aeration valves 411 and 412, which are contained in cleaning manifold840, are operated to allow water to flow from water reservoir 202through line 113, valve 411, valve 404, optionally heater 708, dialysatepump 305, and valve 405 to return to water reservoir 202 throughde-aeration bypass conduit 112, valve 412 and line 114. Before removingsorbent cartridge 703 shown in FIG. 1 from the jumpered flow path shownin FIG. 3, the jumpered circuit is filled with water and a predeterminedexcess volume of water may optionally be flushed through the jumperedflow path 110. To accomplish this, water is metered into the jumperedflow path 110 by water pump 304, purified by sorbent cartridge 703,circulated through the various flow paths, pumps, and valves of thejumpered flow path 110 shown in FIG. 3 and then passed through flushcontrol valve 413 into flush reservoir 841 that is contained withincleaning manifold 840. In an alternative embodiment, a drain connectioncan be substituted for flush reservoir 841. Those skilled in the artwill recognize that the sorbent cartridge may be removed prior to thisstep if provisions are made to complete the fluid circuit, such as byjumpering ports 514 and 513 for the flushing step, and if the sourcewater is sufficiently clean such that no further filtration for use as aflushing fluid or if filtration is provided within the cleaning manifoldsuch as at water inlet ports 509BM and 510BM. Next, the sorbentcartridge is disconnected from jumpered controlled compliant flow path110 and cleaning and/or disinfection concentrate cartridge 720 isconnected at ports 514 and 513. Valves 411 and 412 are positioned toprevent flow through water reservoir 202, while allowing flow throughbase module 803 water intake connection ports 509S and 510S in therecirculating flow path so they can be cleaned and disinfected. Next allpumps shown in FIG. 3 are started and all valves except 413 and 410 arecycled to direct the recirculation fluid through all pathways anddistribute the cleaning and/or disinfection concentrate from cartridge720. Heater 708 is employed to increase the fluid temperature to atemperature that aids disinfection. During the disinfection process thetemperature of the heated cleaning and/or disinfection solution ismonitored by sensors such as 607, 612 and 614 to verify that the fluidtemperature remains within predetermined limits for cleaning and/ordisinfection. Additional temperature sensors and temperature sensorlocations are contemplated by the invention and those skilled in the artwill recognize that the specific location and number of temperaturesensors can be tailored to the requirements of individual embodiments.

Disinfection is controlled by a 4-way interaction between fluidtemperature, type of disinfectant chemical, disinfectant chemicalconcentration, and disinfection time. In one, non-limiting preferredembodiment citric acid is employed as the cleaning and disinfectantchemical at a concentration of approximately 2% by weight. Citric acidis effective to remove mineral scale, is relatively non-toxic andbiocompatible, and readily reconstituted from a dry chemical form. Inone, non-limiting preferred embodiment, the cleaning and disinfectionfluid temperature is 80° C. to 90° C., and the disinfection time attemperature is less than 1 hour. In another, non-limiting embodiment,the cleaning and disinfection fluid temperature is around 85° C. and thedisinfection time is around 20 minutes. One of ordinary skill willunderstand that specific temperature and time parameters will bedependent upon the specific embodiment.

At the conclusion of the cleaning and/or disinfection process, thesystem shuts down and the cleaning manifold 840, disinfectant cartridge720, and disinfectant fluid are left in place for convenience and tokeep the fluid pathways closed to contaminant entry. FIG. 6C shows acutaway of a base module door 802, revealing that the cleaning anddisinfection module 840 may remain in-situ in the stowed configuration.

As illustrated herein, for example in FIGS. 1, 5C and 5G, a base module803 having fluid connection ports 506S, 507S, 508S, 509S, 510S, 515S,516S, 519S, 522S, 523S, 524S, 530S, and 531S is connected to thedisposable and consumable components, optionally organized into thetherapy cassette 820, to complete the controlled compliant flow path110. That is, connections can be made to the base module 803 between adisposable therapy cassette 820, reservoirs such as water reservoir 202,and sorbent cartridge 703 to form a completed jumpered controlledcompliant flow path for preparation of a physiologically compatibledialysate. As illustrated herein, for example FIGS. 3, 5C, 6A, acleaning manifold 840 can be attached to the base module 803 to cleanand disinfect reusable portions of the jumpered controlled compliantflow path 110 separate from other portions of the jumpered controlledcompliant flow path 110 that may be replaced between uses of the system.In other embodiments, a therapy cassette can contain any combination ofone or more disposable or consumable therapy components such as dialyzer701, extracorporeal flow path 100, cartridges 203 and 204, concentratereservoir 205, control reservoir 201, sensors such as ammonia sensor611, and sorbent cartridge 703.

With reference to FIGS. 1, 1D, 1E and 3, the fluid circuitry of thetherapy system may be divided into a number of segments that can becombined to form a completed controlled compliance flow path. Segmentscan be selected from the group consisting of: a first segment having asorbent cartridge 703 or a cleaning and/or disinfection concentratecartridge 720 in fluid communication with the controlled compliant flowpath 110; a second segment having a concentrate pump 306 in fluidcommunication with both a reservoir for addition of a concentratesolution 205 and a conduit of the controlled compliant flow path 110; athird segment containing a degassing module 705 in fluid communicationwith the controlled compliant flow path 110, and a vent control valve410 in fluid communication with a vent port 517 of a degassing module705; a fourth segment having at least one salination pump 307 or atleast one salination valve 406, and a bypass pathway 115 for conveyanceof fluid through a sodium chloride cartridge 203 or a bicarbonatecartridge 204 to a sorbent cartridge 703 without conveyance through adialyzer 701; a fifth segment having a dialyzer 701 with a blood inletport 504 and blood outlet port 505 in fluid communication with anextracorporeal flow path 100 and dialysate inlet port 506 in fluidcommunication with a first microbial filter 706 and dialysate outletport 507 in fluid communication with a one-way valve 403; a sixthsegment that is a bypass flow path 111, functioning as priming andrecirculation loop, for conveying fluid from the sorbent cartridge 703without contacting the dialyzer 701 or passing through a sodium chloridecartridge 203 or a bicarbonate cartridge 204; a seventh segment having acontrol pump 303 in fluid communication with both a control reservoir201 and a conduit of the controlled compliant flow path 110; an eighthsegment having a water pump 304 in fluid communication with both a waterreservoir 202 and a conduit of the controlled compliant flow path 110; aninth segment having a pump 305 in fluid communication with thecontrolled compliant flow path 110, a de-aeration bypass conduit 112 influid communication with at least a conduit of the controlled compliantflow path 110 and an air vent 512, and a fluid intake bypass valve 404to direct or to cause fluid movement of fluid from a port 509 of a waterreservoir 202 through a flow restriction 408 and pump 305 to de-aerate afluid; a tenth segment in fluid communication with both a flushreservoir 841 and a pump 303, 304, 306, or 307 in fluid communicationwith a conduit of the controlled compliant flow path 110; an eleventhsegment in fluid communication with at least a port 509 of a waterreservoir 202, a flow restriction 408 and a fluid intake bypass valve404; a twelfth segment in fluid communication with a port 510 of a waterreservoir 202, a deaeration bypass valve 405 and a pump 305 in fluidcommunication with a conduit of the controlled compliant flow path 110;a thirteenth segment having a hemofilter 731 with blood inlet port 504and blood outlet port 505 in fluid communication with an extracorporealflow path 100 and a filtrate port 537 in fluid communication with aone-way valve 403; a fourteenth segment having a second microbial filter709 in fluid communication with a conduit of an extracorporeal flow path100 and a first microbial filter 706; a fifteenth segment having asecond microbial filter 709 in fluid communication with a conduit of anextracorporeal flow path 100 and a replacement fluid pump 308, thereplacement fluid pump 308 being in fluid communication with a firstmicrobial filter 706 and a dialysate inlet port 506 of a dialyzer 701.

During priming of the system and treatment of a subject, connection ofthe disposable and consumable components, optionally organized intotherapy cassette 820, to the base module 803 connects the secondsegment, the third segment, the fourth segment, the fifth segment andthe seventh segment to the controlled compliant flow path 110 in orderto complete portions of the controlled compliant flow path 110.Installation and connection of sorbent cartridge 703 at ports 513 and514 completes the first segment. The fourth segment is provided to allowfor the presence of sodium cartridge 203 and bicarbonate cartridge 204to allow for the generation of a physiological compatible dialysate fromwater provided from reservoir 202.

Attachment of the cleaning manifold 840 in place of the removabledisposable and consumable therapy components allows for the re-useableportions of the controlled compliant flow path 110 of base module 803 tobe connected into a completed fluid circuit to allow for generation andcirculation of a cleaning and/or disinfection fluid. The connectionsformed by the cleaning manifold 840 are shown by jumpers 860-871 in FIG.3. In particular, a connection can be made between ports 516 and 519 inlieu of the degas module 705, between ports 506 and 507 in lieu of thedialyzer 701, between ports 522, 523 and 524 in lieu of the sodiumchloride cartridge 203 and bicarbonate cartridge 204. Additionalconnections can be made by cleaning manifold 840 to complete a tenthsegment connecting a flush reservoir 841 and a fluid port of the basemodule pump in fluid communication with controlled compliant flow path110, for example port 508 and pump 303, of the base module; an eleventhsegment connecting water reservoir 202 port 509 to base module port509S, and hence to flow restriction 408 and fluid intake bypass valve404 of the base module; and a twelfth segment connecting water reservoir202 port 510 to base module fluid connection port 510S, and hence tobypass conduit 112 and water pump 304 of the base module. The cleaningmanifold 840 attached to the base module 803 completes a jumperedcontrolled compliant flow path 110 wherein connection of the cleaningmanifold 840 to the base module 803 completes or connects the secondsegment, the third segment, the fourth segment, the fifth segment, thetenth segment, the eleventh segment and the twelfth segment to form thecontrolled compliant flow path 110.

The use of the base module 803 and the various fluid connection portsare described in Table 1 below in conjunction with the cleaning manifold840, the disposable and consumable components optionally arranged intotherapy cassette 820, and various jumpered connections that can be madebetween the fluid connection ports. Each fluid connection port can belocated on or connected to one or more of the base module 803, thecleaning manifold 840, or the disposable and consumable componentsoptionally arranged into therapy cassette 820. Table 1 states each fluidport as located on the base module 803 or on another system component.If a fluid connection port is part of the base module 803 as shown in,for example, FIGS. 5C and 5G, the ports location as part of the maincontrolled compliant flow path 110 or the nearest component of the basemodule fluid circuit is indicated under the “Base Module” column. Forexample, the sodium cartridge outlet 522 is indicated to make aconnection local to the salination valve 406 rather than part of themain controlled compliant flow path 110. Each port located on the basemodule 803 is used for one or more connections to the cleaning manifold840 and/or components of therapy cassette 820 or to another systemcomponent such as sorbent inlet 513 and outlet 514, where connection tothe cleaning manifold 840 and/or component of therapy cassette 820 isnot indicated. As described above, sorbent inlet 513 and outlet 514 formconnections with the sorbent cartridge 703 or cleaning and/ordisinfection concentrate cartridge 720.

The connection of any fluid connection port of the base module 803 tothe cleaning manifold 840 or therapy cassette 820 is also indicatedunder the appropriate column. It should be noted that many fluidconnection ports of the base module 803 are used for connection of boththe cleaning manifold 840 and the therapy cassette 820. For example, adialyzer is not used during operation of the cleaning manifold 840.Nevertheless, the dialyzer inlet 506 and outlet 507 ports of the basemodule 803 are in use regardless of whether the cleaning manifold 840 ortherapy cassette 820 is placed. When the components of therapy cassette820 are placed on the base module 803, appropriate connection is made tothe dialyzer, as indicated. When the cleaning manifold 840 is placed onthe base module 803, ports 506 and 507 are still required to complete aflow path for the cleaning solution. As indicated in Table 1, ports 506and 507 both attach to the cleaning manifold 840 and are connected byjumper 860 of the cleaning manifold 840. Ports sharing the same numberedjumper indicate ports that are directly connected by a jumper duringplacement of the cleaning manifold 840.

It is noted that not all ports indicated in Table 1 are located on thebase module 803. For those ports, “no” is indicated under the “BaseModule” column, the relevant connection to the cleaning manifold 840 andthe therapy cassette 820 is indicated. For example, the patient's venousblood access 501 is connected to the venous line 105 of theextracorporeal flow path 100.

Finally, it should be noted that the port and jumper combinations forthe cleaning manifold are a non-limiting exemplary embodiment and othercombinations are contemplated by the invention. Those skilled in the artwill recognize alternate port and jumper combinations that will enable acleaning manifold to form a complete jumpered fluid circuit to flushfluids and circulate a cleaning and/or disinfection fluid through there-usable components of base module 803.

TABLE 1 Connection and Description of Fluid Connection Ports TherapyCleaning Cleaning Connection Base Module Cassette Manifold Manifold orPort Connection Function “S” “T” “M” Jumper 501 Patient's venous bloodNo Venous No No access Line 105 502 Patient's arterial blood No ArterialNo No access Line 102 506 Dialysate inlet of dialyzer Main Dialyzer Yes860 Controlled 701 Inlet compliant flow path 110 507 Dialysate outlet ofdialyzer Main Dialyzer Yes 860 Controlled 701 Outlet compliant flow path110 508 Solution & flush reservoirs Fluid Balance Solution Flush 869,871 Control Pump Reservoir valve 413 303 201 509A Base modulede-aeration Flow No No No circuit water inlet Restriction 408 509BCleaning manifold de- No No Valve 867, 868 aeration circuit water inlet411 510A Base module water inlet and Water Pump No No No de-aerationcircuit water 304 or de- return aeration bypass 112 510B Cleaningmanifold water No No Valve 864, 865 inlet and de-aeration circuit 412water return 513 Sorbent inlet, cleaning Main No No No and/ordisinfection Controlled concentrate inlet compliant flow path 110 514Sorbent outlet, cleaning Main No No No and/or disinfection Controlledconcentrate outlet compliant flow path 110 515 Cation infusate AcidCation Yes 866 concentrate Infusate pump 306 516 Degas module fluidinlet Main Degas Yes 861 Controlled Module compliant 705 Fluid flow path110 Inlet 517 Degas module gas vent Vent control Degas No No outletvalve 410 Module 705 Vent 519 Degas module fluid outlet Main Degas Yes861 Controlled Module compliant 705 Fluid flow path 110 Outlet 520Microbial filter inlet Main No No No Controlled compliant flow path 110521 Microbial filter outlet Main No No No Controlled compliant flow path110 522 Sodium Chloride (NaCl) Salination NaCl Yes 863 cartridge outletValve 406 Cartridge 203 Outlet 523 Sodium bicarbonate Salination NaHC0₃Yes 863 (NaHCO₃) cartridge outlet Valve 406 Cartridge 204 Outlet 524NaCl and NaHCO₃ cartridge Salination NaCl and Yes 863 inlets pump 307NaHC0₃ Cartridge Inlets 530 Ammonia sensor inlet Main Ammonia Yes 862Controlled Sensor 611 compliant Inlet flow path 110 531 Ammonia sensoroutlet Main Ammonia Yes 862 Controlled Sensor 611 compliant Outlet flowpath 110

In FIG. 5A shows an example of the device in a compact configurationthat can be used when the device is out of use, stowed or stored. Theshelf doors 802 have been closed to provide a protective exteriorsurface that can protect interior components of the system while alsocontributing to a transport and storage configuration that has a compactsize and may have a smooth exterior surface. User interface 801 isconfigured in a stowed position, having been nested into an exteriorrecess in the device such that the potentially fragile side of theinterface is protected against the main body of the base unit, leavingonly the protective back and side surfaces of user interface 801exposed, yet positioned flush to the device exterior. This configurationenables a transport and stowage size that can be made compatible withairline carryon luggage size requirements.

In FIG. 5B a retractable handle 803 has been extended and integralwheels 804 are shown that facilitate system transport.

In FIG. 5C hinged shelf doors 802 have been opened to create access tothe fluid connection ports 506S, 507S, 508S, 509S, 510S, 515S, 516S,517S, 519S, 522S, 523S, 524S, 530S, and 531S that are located on themain body of the base module and user interface 801 has been deployed toready the system for setup. Shelf doors 802 create mounting surfaces forthe water reservoir 202 and sorbent cartridge 703.

In FIG. 5D, disposable and consumable therapy components, optionallyorganized into integrated therapy cassette 820, have been installed onthe therapy system after first raising locking lever 805 to allow thesystem to accept the cassette. A simple straight-on translationperpendicular to the view plane of FIG. 5D has placed the cassette onthe system. Locking lever 805 will be pushed down in the direction ofthe dotted arrow to engage the stator of the peristaltic roller bloodpump and at the same time actuate the locking mechanism to lock thecassette 820 in place on the system. The lever 805 shown in FIG. 5D is anon-limiting example and those skilled in the art can readily envisionother mechanisms to engage a peristaltic blood pump stator whilesimultaneously locking the cassette 820 in place.

In FIG. 5E cassette 820 is locked in place. Water reservoir 202 has beenfilled with water and placed in position on a shelf door 802. Waterintake line 113 is connected to base module port 509S and water line 114is connected to base module port 510S. Sorbent cartridge 703 is shown inposition on a shelf door 802 and connected to the controlled compliantflow path at ports 513 and 514. Arterial line 102 and venous line 105are arranged within the therapy cassette 820 and are joined in fluidcommunication to priming overflow reservoir 210 by reversibleconnections.

In FIG. 5F solution reservoir 201 has been unfolded from the therapycassette and mounted on the rear of the therapy system base module 803.The protective exterior surfaces of shelf doors 802 and the protectiveback surface of user interface 801 are shown.

In FIG. 5G, the fluid connection ports 506T, 507T, 508T, 515T, 516T,517T, 519T, 522T, 523T, 524T, 530T, and 531T of the disposable andconsumable therapy components that connect to the base module are shown,as optionally organized into a therapy cassette. The therapy cassettefeatures a dialyzer 701, a degassing module 705, a cation concentratereservoir 205, an ammonia sensing module 611, a dry bicarbonatecartridge 204, and a dry sodium chloride cartridge 203. Arterial line102 and venous line 105 extend from the cassette.

In FIG. 6A the integrated flush fluid storage reservoir 841 of cleaningmanifold 840 that accepts and holds fluids flushed during the cleaningand/or disinfection process is shown. A plurality of jumpers 860-871create fluid pathways that complete the fluid pathways where thedisposable and consumable components of integrated therapy cassette 820have been removed from the fluid circuit prior to cleaning anddisinfection operations. Flush control valve 413 controls flush fluidegress from the jumpered fluid circuit to the integrated flush reservoir841. The flush control valve 413 can be computer or mechanicallyoperated. One of ordinary skill in the art will understand that anysuitable valves for use in fluid lines for dialysis may be used. Thevalves may be one-, two-, three-, or more-way depending on the desireddirection of flow. Again, it will be understood that the presentconfiguration described here is non-limiting wherein many more valve andflow configurations can be designed without departing from the scope ofthe invention. In the described embodiment, valves 411 and 412 allowfluid to be flushed through the connection ports 509S and 510S (notshown) on the base module 803 for thorough cleaning and/or disinfection.A plurality of ports 506M, 507M, 508M, 509AM, 510AM, 515M, 516M, 519M,522M, 523M, 524M, 530M, and 531M having integral fluid seals connect tocorresponding ports of the base module 803 when the cleaning manifold840 is placed on the base module after the therapy cassette 820 has beenremoved.

In FIG. 6B, a cleaning manifold 840 with integral jumpers 860-871, flushcontrol valves 411-413 and integral flushed fluid reservoir 841 is shownin place on the therapy system. Cleaning and/or disinfection concentratecartridge 720 is shown connected at ports 513 and 514 to the controlledcompliant flow path in place of sorbent cartridge 703 (not shown in thisfigure).

FIG. 6C shows an exterior view of the system after cleaning and/ordisinfection has been completed. A portion of shelf door 802 is cut awayto reveal that the cleaning manifold 840 remains in place on the systemand the cleaning and/or disinfection fluid remains in the fluid circuit.Shelf doors 802 have been closed and user interface 801 stowed.

FIG. 7A shows one possible section detail for a mating fluid portconnection between a removable disposable or consumable therapycomponent arranged in a therapy cassette 820 and a fluid pathway of thesystem base module 803. The mating fluid port connection utilizes a maleinto female configuration such that the removable therapy componentportion of the connection 830 is male and has an integral seal 831 thatseals against the internal surface of the female port 832 that formssystem base module 803 portion of the fluid interconnect. Connectionports 830 and 832 respectively have male and female configurations thatdo not limit the configurations to having only round cross sections. Oneof ordinary skill in the art will understand that other shapes such asoval cross sections can be configured to fit together as a male andfemale connection wherein such alternative configurations arecontemplated by the present invention. Additionally, other sealingconfigurations known to those of ordinary skill in the art can be used.For example, sealing systems containing one or more O-rings, X-rings,Quad rings, lip seals, spring energized seals can be used. Moreover, oneof ordinary skill can use replacements for the removable therapycomponent portion of the connection 830 using any suitable sealingsystems and/or methods known by those of ordinary skill in the art. Toprovide for a secure seal, a fresh set of seals can be provided by theremovable therapy component conduit portion 830 each time a newdisposable or consumable component is installed onto the base module803. It is further contemplated by the invention that check valves knownto those of ordinary skill in the art (not shown) can be added to eitherthe male or female half of the connection port to prevent fluid flowwhen the port is disconnected.

In FIG. 7B, one possible female fluid connection port 843 of thecleaning and disinfection manifold 840 is shown in place on the basemodule 803 port 832. The base module 803 portion of the fluid connectionis 832 and is male and fits inside the female port 843 of cleaningmanifold 840. Connection ports 843 and 832 respectively have female andmale configurations that do not limit them to having only round crosssections. For example, one of ordinary skill in the art can envisionother shapes, such as oval cross sections that can be configured to fittogether as a male and female connections for use in the presentinvention. The seals 845 for this connection are provided on thecleaning manifold port 843. Various configurations and materials for theseals 845 are contemplated by the invention. The double seals 845 areintended to be illustrative in nature and not intended to limit thescope of the present invention. Those of ordinary skill in the art canenvision other possible seal configurations such as O-rings, X-Rings,Quad-rings, lip seals and spring energized seals.

It will be recognized by one skilled in the art that the portconfigurations shown in FIGS. 7A and 7B are complimentary and work incombination to ensure that all fluid port surfaces that may contact thetherapy solution, or dialysate will always be reliably exposed to thecleaning and/or disinfection fluid. Further, the external end surfacesof the base module 803 fluid port tubes 832 are also exposed to thecleaning and/or disinfection fluid, which ensures that microbial growthis not allowed to be present at the ends of the base module 803 fluidconnection port tubes 832 and become transferred to the therapy solutioncontacting end surfaces of the removable therapy component maleconnector 830. The specific placement of the ports need not exactlyconform to those depicted where other configurations for achieving theintended purposes of the invention can be used and many alternativeconfigurations can be envisioned without departing from the scope of theinvention.

A method of circulating blood and a dialysate through a dialyzer using ahemodialysis device having a controlled compliance flow path and havinga range of positions where the conditioning pathway 115 outflow can beinfused into the main controlled compliant flow path is shown in FIG. 8,for example, using the hemodialysis device illustrated in FIG. 1Arepresenting one embodiment of the disposable and consumable therapycomponents only connected in fluid communication with one segment of adialysate flow path. As shown in FIG. 1A, the fluid connection ports506T, 507T, 508T, 522T, 523T, 524T, 514T, 513T, 515T, 516T, 517T, 519T,530T, 531T, 520T, and 521T can connect to the corresponding fluid portsof a base module. The removable disposable and consumable therapycomponents in the present, non-limiting examples include a degassingmodule 705, an ammonia sensing module 611, a dry bicarbonate cartridge204, a dry sodium chloride cartridge 203, a cation concentrate reservoir205, a solution reservoir 201, a dialyzer 701, and an extracorporealflow path 100. However, additional permutations or groupings ofcomponents are contemplated, such as the dialyzer and dry bicarbonatecartridge.

With reference to FIG. 8, in the first step of the method of circulatingblood and a dialysate through a dialyzer 900 a preliminary setupprocedure 901 can be performed to change the configuration of thehemodialysis device from a stowed or transport configuration to an openand ready configuration. In the next step, a therapy setup procedure canbe performed 902 to further prepare the hemodialysis device for ahemodialysis therapy session by attaching the components and materialsrequired to perform therapy. Next, a priming procedure can be performed903 to initially fill a controlled compliance flow path andextracorporeal circuit with a physiologically compatible solution, suchas a dialysate. Then, a therapy procedure is performed 904 to circulateblood and the dialysate through a dialyzer. When the therapy has beencompleted, a rinse-back procedure can be performed 905 to return theblood from the extracorporeal flow path. Then, an evacuation procedurecan be performed 906 to remove fluid from the extracorporeal flow pathand controlled compliant flow path. Finally, a cleaning and disinfectionprocedure can be performed 907 to prepare the hemodialysis device forstorage before a future dialysis session.

The solutions or fluids required for a hemodialysis therapy session caninclude a fluid to prime the dialysate flow path, a fluid to prime adialyzer and extracorporeal flow path, a fluid to provide a bolusinfusion to a subject receiving therapy, and a fluid to rinse bloodcontained in the dialyzer and extracorporeal flow path back to thesubject at completion of therapy. The solutions or fluids required for ahemofiltration therapy session can include a fluid to prime the filtrateflow path, a fluid to prime a hemofilter and extracorporeal flow path, afluid to provide a bolus infusion to a subject receiving therapy, areplacement fluid, and a fluid to rinse blood contained in thehemofilter and extracorporeal flow path back to the subject atcompletion of therapy. The solutions or fluids required for ahemodiafiltration therapy session can include a fluid to prime thedialysate flow path, a fluid to prime a dialyzer and extracorporeal flowpath, a fluid to provide a bolus infusion to a subject receivingtherapy, a replacement fluid, and a fluid to rinse blood contained inthe dialyzer and extracorporeal flow path back to the subject atcompletion of therapy. The procedures of method 900 will describe thesteps to produce fluids that are physiologically compatible in terms ofchemistry and having microbiological purity for these uses.

Further, a detailed sequence of steps will be disclosed for each of theindividual steps of the method 900. With reference to FIG. 9, thepreliminary setup procedure 901 to configure the hemodialysis deviceequipment can be performed by a user in conjunction with simultaneousmonitoring by the hemodialysis system to verify and confirm correctsetup of the equipment. In some embodiments the user can be a therapysubject.

Referring to FIG. 9, at initiation of system setup for the next therapysession, the user can enter a request to remove the input cleaningmanifold 911, which generally remains installed on the base modulebetween therapy sessions to ensure the fluid pathways remain free ofcontamination. For example, in an embodiment shown in FIGS. 2 and 5C, auser can initiate the preliminary setup procedure by turning on systempower and selecting Setup Mode via user interface 801. The user furthercan enter a request through user interface 801 to remove cleaningmanifold 840 and start the setup process for a therapy session. Thesystem or device then can cycle the pumps and valves in sequence todrain the cleaning and/or disinfection solution from the fluid pathwaysand components of controlled compliant flow path 110, conditioning flowpath 115 through pump 307 and valve 406, bypass flow path 111, meteringpumps 303, 304 and 306 the cleaning and/or disinfection concentratecartridge, and the cleaning manifold jumper lumens. The drained fluid iscollected in integrated reservoir 841 contained in cleaning manifold840. Optionally, in some embodiments, water reservoir 202 can be filledwith water and connected to cleaning manifold ports 509BM and 510BM toallow fresh water flushing of the cleaning and/or disinfection solutionas a first part of the fluid draining step.

In the next step, the user verifies that the cleaning and/ordisinfection solution has been drained from a cleaning and/ordisinfection cartridge and a cleaning manifold 912 in FIG. 9.Alternatively, in any embodiment the system can return a message to theuser via user interface 801 in FIGS. 2 and 5C that the user may nowremove cleaning manifold 840 and cleaning and/or disinfectionconcentrate cartridge 720. For example, and throughout operation, thesystem may intermittently activate sensors to confirm removal or correctloading of components and materials. In any embodiment, the hemodialysisdevice can communicate through visual, audible, or tactile signals tothe user during the process to confirm successful completion of setuptasks, or to provide corrective feedback to complete the task.

In the next step, the user removes the cleaning manifold 913 and removescleaning and/or disinfection concentrate cartridge 914. The user candrain the contents of cleaning manifold reservoir 915, for example, bygravity, into a suitable disposal and the cleaning manifold 840 can beretained for re-use at completion of the next therapy session.

Referring now to FIG. 10, therapy setup procedure 902 begins in step 920and the user can install a the disposable and consumable therapycomponents 921. For example, referring to FIG. 1, arterial pinch valve402 and venous pinch valve 401 can be opened so that blood lines 102 and105 of extracorporeal flow path 100 can be inserted. With reference toFIGS. 5C and 5D, the user can place disposable and consumable componentsthat are optionally arranged as therapy cassette 820 onto the inventionand engage latch mechanism 805 wherein the arterial pinch valve 402 andvenous pinch valve 401 are reset to the normally closed position. In anyembodiment, sensors may be used to confirm that the disposable andconsumable components or therapy cassette 820 are properly engaged anduser interface 801 can signal to user that task is successfullycompleted, or provide corrective feedback to complete the task.

The user then can install the solution reservoir 922. Referring to FIGS.1 and 5E, if a solution reservoir 201 has been included in a cassettesuch as 820, user can re-position solution reservoir 201 from therapycassette 820 and place it in the operating position on system. In anyembodiment, optional sensors may be used to confirm the solutionreservoir is properly placed and the user interface can signal to theuser that the solution reservoir installation task is successfullycompleted, or can provide corrective feedback to complete the task.

Next, the user can install the sorbent cartridge 923 as shown in FIG.10. In an embodiment shown in FIGS. 1 and 5E, the user can install thesorbent cartridge 703 on system and connect the sorbent cartridge 703inlet and outlet ports 513, 514 to the controlled compliant flow pathconnectors, respectively. In any embodiment, sensors may be used toconfirm the sorbent cartridge has been properly engaged and signals sentto user that task is successfully completed such that the sensors canprovide corrective feedback to complete the task.

Then, the user can install the water reservoir 924 as shown in FIG. 10.In an embodiment illustrated in FIGS. 1 and 5D, the user can fill waterreservoir 202 with potable water or other types of water suitable foruse in the present invention, place it on the therapy system, andconnect it to the fluid intake ports 509S and 510S of the system. In anyembodiment, the user can transport water including potable water to thewater reservoir 202 and fill it in place on the system. In anyembodiment, sensors may be used to confirm that the water reservoir 202is properly filled and engaged wherein the user interface signals touser that the water reservoir installation task is successfullycompleted, or provides corrective feedback to complete the task.

In the next step, the user can verify that the setup sequence iscomplete 925. In any embodiment, the user interface can display amessage that the setup sequence has been successfully completed andprompt the user for authorization to initiate a system priming sequence.

A detailed priming procedure is shown in FIG. 11. First, the user caninitiate the priming procedure 931 to fill and prime a hemodialysisdevice dialysate flow path and extracorporeal flow path. In anyembodiment, the filling and priming process can be automaticallyperformed by the hemodialysis device. For example, in an embodimentshown in FIGS. 2 and 5E, the user can initiate the priming sequencethrough a user interface and the fluid circuit priming sequence canproceed automatically under control of a controller. Next, the devicecan confirm it has entered the dialysate priming mode 932, for example,by displaying a message on the user interface.

In the next step, a de-aeration procedure can be performed 933. Forexample, in an embodiment corresponding to FIG. 1C, the valves statescan be switched or positioned to create a de-aeration recirculationfluid circuit loop. Fluid intake bypass valve 404 can open a flow pathconnecting water intake line 113 to the controlled compliant flow pathin the direction of the heater 708 only, and de-aeration bypass valve405 can open a flow path from the dialysate pump 305 to the de-aerationbypass conduit 112 only. In this example, the water intake pump 304 isnot operated, thus causing any flow through de-aeration bypass conduit112 to be directed back to the water reservoir 202 through water line114.

Further, the dialysate pump 305 can be operated to pull water into thecircuit from water reservoir 202 through flow restriction 408 at a flowrate such that the absolute pressure of the fluid is reducedsufficiently, by the, within the restriction to release a majority ofthe dissolved air from solution and convert it to air bubbles that canbe vented from the circuit through vent opening 512 in water reservoir202 as the water returns to water reservoir 202. At the same time,optionally, heater 708 can be operated to heat the water flowing throughthe recirculating de-aeration loop to a predetermined temperature,further reducing the solubility of air in water and enhancing thede-aeration process. Optionally, the water can be circulated and heatedin the de-aeration loop for a pre-determined time period sufficient tode-aerate the water. In certain embodiments, an optional air bubbledetector 608 can be positioned in the de-aeration fluid loop to monitorand confirm that the air is sufficiently removed from the water. Whenair bubbles are no longer observed passing a bubble detector after apredetermined time, the water is sufficiently degassed to continue tothe next step of the process.

In the next step, a dialyzer bypass loop priming procedure can beperformed 934 to mix a physiologic solution and store the solution in areservoir. For example, in an embodiment corresponding to FIG. 1, thevalve states can be set to create the mixing and filling fluid circuit.Fluid intake bypass valve 404 closes the water inlet path through flowrestrictor 408 and opens the controlled compliant flow path betweenpumps 303 and 304. De-aeration bypass valve 405 closes the de-aerationbypass conduit 112 and opens the controlled compliant flow path fromdialysate pump 305 through sorbent cartridge 703, and dialyzer bypassvalve 407 is set to direct flow from the outlet port 519 of degassingmodule 705 to the bypass flow path 111. Passing water through thematerials contained in the sorbent cartridge can purify the water byremoving organic, inorganic and microbial contamination from the wateras the water passes through the sorbent cartridge.

With reference to FIG. 1, the dialysate loop can initially be filled aswater intake pump 304 and dialysate pump 305 begin pumping to intakewater and recirculate it through the bypass flow path 111. Water pump304 can be operated until the fluid pressure measured at pressure sensor610 rises to a predetermined level. The rate of water pump 304 is thencontrolled to maintain the fluid pressure within a predetermined rangeby pumping in additional fluid as air is exhausted from the fluidcircuit through degassing module 705. Bubble detector 608 can bemonitored and the recirculation continued until no more air is detectedin the line. In any embodiment, air from the operating portion of thecontrolled compliant flow path can be trapped in degas module 705 andexhausted through vent port 517 and vent control valve 410 during thissequence.

In the next step, a buffering loop priming procedure can be performed935. For example, in an embodiment in accordance with FIG. 1, in orderto prime the dry sodium bicarbonate cartridge 204, salination valve 406can open a flow path through outlet port 523 of bicarbonate cartridge204 to the junction with the controlled compliant flow path between pump303 and pump 304, and the salination pump 307 can be started while waterintake pump 304 and dialysate pump 305 continue to operate as per theprevious sequence. The buffering loop priming procedure is concludedwhen the air bubbles have passed bubble detector 608 and a conductivityincrease is observed at conductivity sensor 613. In any embodiment, airfrom the bicarbonate cartridge 204 is moved to degas module 705,trapped, and exhausted from the fluid circuit at vent port 517 throughvent control valve 410 during this sequence.

Continuing to the next step, a salination loop priming procedure can beperformed 936. For example, in an embodiment shown in FIG. 1, in orderto prime the dry sodium chloride cartridge 203, salination valve 406 canopen a flow path through outlet port 522 of sodium chloride cartridge203 to the junction with the controlled compliant flow path between pump303 and pump 304, and the water intake pump 304 and the dialysate pump305 continue to operate according to the previously described sequence.The salination loop priming procedure is concluded when the air bubbleshave passed bubble detector 608 and the conductivity reading observed atconductivity sensor 613 indicates that the desired physiologic sodiumconcentration level in the solution has been reached. In any embodiment,air from the sodium chloride cartridge 203 can be removed by thedegassing module 705, trapped, and exhausted from the fluid circuitthrough vent port 517 and vent control valve 410 during this sequence.

In the next step, a physiologic solution preparation can be performed937. For example, the system can add a concentration of approximately0.9% by weight of sodium chloride to the water that has been firstpurified by passing through the sorbent cartridge to produce aphysiologically compatible solution for priming a hemodialysis system. Asolution of this composition will be recognized by those of skill in theart as a physiologically compatible solution for contacting blood aspart of a renal replacement therapy delivery process and is a solutioncommonly employed for priming a dialyzer and extracorporeal circuit andalso as a solution for blood rinse back to a subject from theextracorporeal circuit at completion of a therapy session. For example,in an embodiment in accordance with FIG. 1, in order to mix aphysiologic priming solution and store the physiologic solution insolution reservoir 201, fluid balance control pump 303 can be operatedto move fluid from the fluid circuit to solution reservoir 201 whileoperating water intake pump 304 to pull water into the circuit at thesame rate. The salination valve 406 can direct flow through the sodiumchloride cartridge 203, and the salination pump 307 rate can be adjustedto a predetermined proportion of the water intake pump 304 rate toproduce the desired solution sodium concentration while monitoring theconductivity of the mixed solution at conductivity sensor 613.

The rate of salination pump 307 can be adjusted according to theconductivity readings to maintain the desired solution sodiumconcentration, wherein the salination pump rate is the volumetric flowrate of fluid passing through the conditioning conduit flow path 115. Inany embodiment, during this sequence the salination valve 406 can beperiodically switched or positioned to direct flow through bicarbonatecartridge 204 to infuse a desired amount of bicarbonate buffer into thesolution. The physiologic solution preparation can be continued until apredetermined volume of solution has been produced and reserved insolution reservoir 201. For example, the total volume of requiredphysiologic solution can be determined as the sum of the priming volumeof dialyzer 701, the priming volume of the extracorporeal flow path 100,and a blood rinse-back reserve volume to be used at the end of thetherapy session, and a predetermined fluid bolus reserve volume. Thefluid bolus reserve volume can be held in reserve as aphysiological-compatible fluid bolus infusion reserve volume to returnto the subject if needed during therapy, such as for treatment ofepisodic intradialytic hypotension. Optionally, an additionalpredetermined volume can be prepared and reserved as a flushing fluidfor a dialyzer and/or an extracorporeal flow path in reservoir 201 if avolume for additional rinsing of a dialyzer or an extracorporeal flowpath is needed, such as in the case where a contaminant such as residualsterilant from the dialyzer manufacturing process is to be rinsed from adialyzer and/or extracorporeal circuit or flow path.

Then, a dialyzer loop priming procedure can be performed 938. Forexample, with reference to FIG. 1, in order to prime the remainder ofthe controlled compliant flow path and dialyzer, the water intake pump304 and salination pump 307 can be stopped while bypass valve 407 is setto direct flow through the dialyzer and fluid balance control pump 303operates to add solution volume from solution reservoir 201 back to thecontrolled compliant flow path 110 while dialysate pump 305 continues tooperate. The trans-membrane pressure monitored by dialysate pressuresensors 606 and venous pressure 604 and fluid balance control pump 303rate is controlled to ensure that the hollow fibers in the dialyzer 701are not collapsed or damaged by exceeding their pressure capacity.

In any embodiment, the therapy solution can be infused during thisprocess with bicarbonate and electrolytes (for example, potassium,magnesium, glucose or calcium) per a dialysate prescription by switchingsalination valve 406 to bicarbonate cartridge 204 flow path andoperating the salination pump 307 to infuse bicarbonate from cartridge204, and operating acid concentrate pump 306 to infuse electrolytes fromcation concentrate reservoir 205 to the priming solution per the desireddialysate prescription. In any embodiment, sorbent cartridge 703 canremove the majority of bacteria and endotoxin from the solution as itpasses through the sorbent cartridge. Residual bacterial and endotoxinare removed from the solution prior to entering the dialyzer by firstpassing through endotoxin retentive microbial filter 706 located in thefluid circuit prior to the dialyzer inlet 506. Air from the remainder ofthe controlled compliant flow path and dialyzer is trapped in degasmodule 705 and exhausted through vent port 517 and vent control valve410 during this sequence. The dialyzer priming procedure can continuefor a predetermined time and until air bubbles are not observed atbubble detector 608, indicating that the controlled compliant flow pathis completely filled.

In the next step, a venous loop priming procedure can be performed 939.The physiologically compatible solution that has been passed into thedialyzer by the preceding steps can first be purified by passing thefluid through the sorbent cartridge wherein a physiologically compatiblelevel of at least sodium chloride, for example approximately 0.9% byweight, has been added to the purified water. The solution can then bepassed through a microbial filter 706 for removal of residual microbialcontamination from the solution. When the solution flows through thedialyzer membrane to the blood, the dialyzer membrane 702 can serve as afinal, redundant microbial filter. Thus, a physiologically compatiblesolution for contacting blood having a necessary microbiological purityis unexpectedly provided from potable or tap water by the presentinvention. For example, in an embodiment in accordance with FIG. 1, thepumps and valves in the dialysate loop can continue to operate asdescribed in the previous sequence moving solution from the solutionreservoir 201 to the controlled compliant volume fluid path ofcontrolled compliant flow path 110 which is now filled, thus causing thesolution to further back filter across the dialysis membrane 702 fromthe dialysate compartment to the blood compartment. In any embodiment,the dialyzer membrane 702 provides a redundant barrier to preventbacteria and endotoxin from entering the blood compartment duringpriming of the extracorporeal flow path.

As the pumps and valves of the dialysate loop continue to operate in themanner described, arterial pinch valve 402 remains closed and venouspinch valve 401 is opened. Referring also to FIG. 4A, this action allowssolution to fill the lumen of venous line 105 and displace the air outthrough venous connector 501 to an overflow bag 210 attached through atee fitting 550 at the junction between arterial line connector 502 andvenous line connector 501. In the case of the alternative configurationshown in FIG. 4B, this action allows solution to fill the lumen ofvenous line 105 and displace air out of a hydrophobic vent membrane 560at the junction of arterial line connector 502 and venous line connector501. In the further case of alternative configuration shown in FIG. 4C,this action allows solution to fill the lumen of venous line 105 anddisplace air out through connector 501 into overflow bag 210. Thisprocess continues until a volume of fluid sufficient to displace theinternal volume of venous line 105 and any desired additional flushvolume has been pumped and no further bubbles are being detected atair-fluid (bubble) detector 603. Then venous pinch valve 401 is closed.Alternatively, in the example shown in FIG. 4, the operation can becontinued until the pressure reading increase at venous pressure sensor604 indicates that the venous line 105 has been filled and no furtherair is detected by venous bubble detector 603.

Next, an arterial loop priming procedure can be performed 940 asdescribed in FIG. 11. For example, in an embodiment corresponding toFIG. 1, as the dialysate loop pumps and valves continue to operate inthe manner described in the previous step, arterial pinch valve 402 isnow opened and blood pump 302 is operated in reverse first to completefilling of the dialyzer blood compartment and finally arterial line 102.Referring also to FIG. 4A, this action allows solution to fill the lumenof arterial line 102 and displace the air out through arterial connector502 to an overflow bag 210 attached through a tee fitting 550 at thejunction between arterial line connector 502 and venous line connector501. In the case of the alternative configuration shown in FIG. 4B, thisaction allows solution to fill the lumen of arterial line 102 anddisplace air out of a hydrophobic vent membrane 560 at the junction ofarterial line connector 502 and venous line connector 501. In thefurther case of alternative configuration shown in FIG. 4C, this actionallows solution to fill the lumen of arterial line 102 and displace airout through connector 502 into overflow bag 210.

Blood pump 302 continues to operate until the desired volume of fluidhas been pumped through arterial line 102 and no further bubbles aredetected at arterial bubble detector 601. Then the arterial pinch valve402 is closed. Alternatively, in any embodiment blood pump 302 can beoperated until the pressure reading increase at arterial pressure sensor602 indicates that the arterial line 102 has been filled and no furtherair is detected by arterial bubble detector 601, at which time thesystem stops all pumps and maintains arterial pinch valve 402 and venouspinch valve 401 in the closed position.

In an alternative configuration shown in FIG. 4C, blood pump 302 can beoperated to recirculate the solution that has filled extracorporealcircuit 100 by the actions of steps 938, 939 and 940 for a predeterminedtime through the dialyzer and extracorporeal circuit to rinsecontaminants from the dialyzer and extracorporeal circuit such asresidual sterilant or particulate residue that can be present in certaincommercially available dialyzers and extracorporeal circuits. Followinga predetermined recirculation, a volume for additional rinsing of adialyzer or an extracorporeal flow path can be conveyed from reservoir201 through the controlled compliant flow path to flush the contaminantsand contaminated solution to overflow bag 210.

Then, the system can confirm that the hemodialysis device is preparedfor a therapy session 941. For example, the user interface can display amessage to notify the user that priming is complete and system is readyfor a therapy session.

During steps 938, 939 and 940 the minimum volume of solution required tofill the blood compartment of the dialyzer and the extracorporealcircuit 100 can be referred to as the void volume or a priming volume ofthe extracorporeal flow path.

FIG. 12 shows a therapy procedure 904 in accordance with the invention.The user can initiate the therapy procedure 950 by preparing bloodaccess 951 per the patient's normal blood access preparation procedure.Then, blood can be drawn into the arterial and venous lines of anextracorporeal flow path 952. For example, in an embodiment shown inFIGS. 1, and 4A, 4B or 4C, the user can separate the arterial lineconnector 502 from the priming connection and connects arterial line 102of the extracorporeal flow path 100 to the arterial blood access 104 atarterial line connector 502. The user can then prompt the hemodialysisdevice through user interface 801 to start blood flow.

Blood pump 302 can be operated with the arterial pinch valve 402 andvenous pinch valve 401 open. Blood displaces the priming solution inextracorporeal flow path 100, first through arterial line 102, nextthrough dialyzer 701, and then out through the venous line at 501 intooverflow reservoir 210. Blood pump 302 stops when a volume of fluidapproximately equal to the internal volume of the extracorporeal flowpath has been displaced into priming overflow reservoir 210 by thepumped blood. Alternatively, the displaced priming solution can bedischarged into a suitable container or a drain. The user can connectvenous line 105 of extracorporeal flow path 100 to the patient's venousblood access line 103 at connector 501.

Alternatively, in any embodiment all of the priming solution can beretained in the system without requiring an overflow bag or dischargeinto a collection container. For example, the user can separate venousline 105 of extracorporeal flow path 100 from tee fitting 550 of thepriming overflow reservoir 210 or, in some embodiments, from hydrophobicvent 560, and connects patient's venous blood access 103 at connector501. The user further can prompt the system through the user interfaceto start venous blood flow. The system can open venous pinch valve 401and switches valve 407 to bypass mode or, in some embodiments, closedegassing vent control valve 410 to prevent air from being drawn intothe system by sub-atmospheric pressure in controlled compliant flow path110 through port 517 and the hydrophobic vent membrane of degassingmodule 705. Fluid balance control pump 303 can be operated to pull thepriming solution across dialysis membrane 702 from the blood compartmentto the dialysate compartment and into solution reservoir 201. Fluidcontrol pump 303 continues to operate until a predetermined volume ofsolution approximately equal to the internal volume of venous line 105has pumped across dialysis membrane 702 to solution reservoir 201. Thenfluid control pump 303 stops and venous pinch valve 401 closes.

Next in any embodiment wherein all of the priming solution can beretained in the system without requiring an overflow bag or dischargeinto a collection container, the user interface 801 can prompt the userto connect arterial line 102 of extracorporeal flow path 100 to thearterial line 104 of the patient's blood access at connector 502, andthe user can connect arterial line 102 of extracorporeal flow path 100to the arterial connector of the patient's blood access line 104 atconnector 502. In any embodiment, the user can confirm through userinterface 801 that the arterial blood access is connected. The systemcan open arterial pinch valve 402 and start blood pump 302 and fluidbalance control pump 303 at equal pumping rates to displace a volume ofsolution approximately equal to the sum of the internal volumes ofarterial line 102 and dialyzer 701 blood compartment across dialysismembrane 702 and into the solution reservoir 201. Then the fluid balancecontrol pump 303 can be stopped and venous pinch valve 401 opened toallow blood pump 302 to pump blood through the complete extracorporealflow path and back to the subject through venous blood access line 103.

In the next step, a therapy sequence can be executed 953. For example, atherapy process control algorithm can be executed to accomplish thedialysis prescription as follows: The dialysate pump 305, the blood pump302 and the heparin pump 301 each can be operated at their respectiveprescribed flow rates. Dialysate temperature can be controlled by heater708 in closed loop with temperature measurements from a temperaturesensor, such as sensor 612, or any appropriate location in controlledcompliant flow path 110. In certain embodiments, the acid concentratepump 306 can be operated at a controlled ratio to the dialysate flowrate to infuse the dialysate with the proper concentration of cations,such as K⁺, Mg⁺⁺, Ca⁺⁺ from cation concentrate reservoir 205. Othersolutes, for example glucose and/or acetic acid, may also be included inthe cation concentrate in reservoir 205 as per the dialysisprescription, and thereby added at the prescribed concentration to thedialysate by this means, and salination valve 406 can be operated todirect flow through bicarbonate cartridge 204 and the salination pump307 is operated at a controlled rate to infuse the dialysate with theprescribed level of bicarbonate buffer. Control of the dialysate sodiumlevel can be accomplished by sensing conductivity at conductivity sensor613 and operating water pump 304 to add water to reduce sodium level or,alternatively, switching salination valve 406 to direct flow throughsodium chloride cartridge 203 and operating salination pump 307 toinfuse sodium chloride concentrate into the dialysate to increase thesodium level, while control of the patient fluid removal rate isaccomplished by controlling the fluid balance control pump 303. When thecontrol pump 303 withdraws fluid volume from the controlled volumecontrolled compliant flow path 110 to the solution reservoir 201 inexcess of the volumes added by pumps 304 and 306 a volume of fluid equalto the excess amount is drawn from the patient's blood across dialysismembrane 702 to controlled compliant flow path 110.

Because the controlled compliant flow path 110 has a fixed volume, netfluid removal is controlled and determined according to the followingformula:Patient Fluid Balance+Fluid Balance Control Pump+Water Pump+Acid Conc.pump Σ_(i=0) ^(n) X _(i)=0

One skilled in the art will recognize that both constant and varyingprofiles of patient ultrafiltration rate and dialysate sodium levels canbe accomplished through this algorithm. As provided herein, the term Xrefers to the volumetric flow rate of a pump where the number of pumpscan range for n from 0 to 20. The term “n from 0 to 20” means anyinteger value of 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, or 20.

In any embodiment, a fluid bolus can optionally be added 955. Forexample, in an embodiment in accordance with FIG. 1, the user mayrequest a fluid bolus through user interface 801. Fluid bolus isprovided to the subject at a controlled rate and to a controlled totalvolume by changing the rate of fluid balance control pump 303 such thatnet fluid is added to controlled compliant flow path 110 from controlreservoir 201 according to the preceding formula. Because controlledcompliant flow path 110 has a substantially inflexible void volume, anynet fluid added to controlled compliant flow path 110 will be passedacross dialysis membrane 702 to the blood compartment and the patient.Check valve 403 ensures that any fluid added to controlled compliantflow path 110 cannot enter the dialyzer through port 507, but rather,the bolus solution is forced to travel only toward the sorbent cartridge703 and is purified by first flowing through sorbent cartridge 703, gasbubbles are removed by flowing through degassing module 705 and thenthrough microbial filter 706 before passing into the dialyzer. Finally,the fluid can first pass through the dialyzer membrane before contactingthe blood, with the dialyzer membrane serving as a redundant filtrationstep to ensure microbial purity of the fluid volume passing to theblood.

In other embodiments, such as the system for hemofiltration shown inFIG. 1D and the system for hemodiafiltration shown in FIG. 1E, aphysiologically compatible solution for infusion to a subject isproduced by passing the fluid exiting microbial filter 706 through anadditional microbial filter 709 that can act as a redundant filtrationstep to ensure microbial purity of the fluid before it entersextracorporeal circuit 100 at port 538 and is passed to the subject.

The sodium level can be assessed by monitoring conductivity at sensor613 and if the sodium level of the bolus solution deviates from thedesired value, the solution is sent through bypass flow path 111 byvalve 407 and circulated until the sodium level is adjusted by eitheradding water from reservoir 202 through water pump 304 to lower sodiumconcentration in the bolus solution by dilution, or by infusing sodiumthrough sodium chloride cartridge 203 to increase sodium concentrationin the bolus solution. In any embodiment, the bolus fluid can bere-infused with electrolytes by cation concentrate from reservoir 205metered by acid concentrate pump 306. The solution is further filteredthrough microbial filter 706 to remove residual microorganisms andendotoxin, and next across dialysis membrane 702 to the bloodcompartment and to the patient. In any embodiment, dialysis membrane 702provides a redundant microbiological barrier between the dialysatecompartment and the blood compartment.

The therapy process continues until the dialysis prescription iscompleted 955. Alternatively, the user can request to end the therapyprocess. If therapy is successfully completed per the dialysisprescription, the system can provide notification through user interface801 that the therapy session is completed.

FIG. 13 shows a blood rinse-back procedure 905 in accordance with theinvention. The user can initiate the rinse-back procedure 960, forexample, by entering a request through the user interface for bloodrinse back or blood rinse back can begin automatically at the conclusionof a therapy session. Through operations as described in precedingsteps, the fluid in the controlled compliant flow loop 110 and reservoir201 can be comprised of filtrate from the blood of the subject and aphysiologically compatible solution that has been has been firstpurified by passing through the sorbent cartridge that has aphysiologically compatible level of at least sodium chloride, forexample approximately 140 mEq/L. Before entering the dialyzer, the fluidis further passed through microbial filter 706 for removal of residualmicrobial contamination from the fluid. When the solution is furtherpassed through the dialyzer membrane to the blood, the dialyzer membraneserves as a final, redundant microbial filter. Thus, a physiologicallycompatible solution for blood rinse back to a subject can be providedwith necessary microbiological purity. In any embodiment, the user cancontrol the sequence of arterial line 102 and venous line 105 rinse backby selecting through user interface 801 which line to rinse back first.Then, the arterial line can be rinsed back 961. For example, in anembodiment corresponding to FIGS. 1 and 2, blood can be rinsed back tothe patient from arterial line 102 by operating the fluid control pump303 to add fluid back to controlled compliant flow path 110 fromsolution reservoir 201 to cause solution to move from the controlledcompliant flow path 110 across dialysis membrane 702 to the bloodcompartment. Venous pinch valve 401 can be closed and blood pump 302 isoperated in reverse direction at the same rate as fluid control pump 303is adding solution to controlled compliant flow path 110. In thismanner, a solution volume sufficient to rinse the volume of blood fromthe blood compartment of dialyzer 701 and arterial line 102 back to thepatient is pumped and then fluid balance control pump 303 and blood pump302 are stopped. In any embodiment, the user can prompt through the userinterface to return an additional increment of fluid for further rinseback of arterial line 102, or acknowledge that arterial line 102 issufficiently rinsed back. When the user confirms through user interface801 that arterial line 102 is sufficiently rinsed back, arterial pinchvalve 402 closes to prevent further fluid ingress or egress througharterial blood access line 104.

Next, the venous line can be rinsed back 962 as described in FIG. 13.Blood can be rinsed back to the patient from the venous line byoperating fluid balance control pump 303 in an embodiment correspondingto FIGS. 1 and 2 to add solution back to controlled compliant flow path110 from solution reservoir 201 to cause solution to move from thecontrolled compliant flow path 110 across dialysis membrane 702 to theblood compartment. Venous pinch valve 401 is opened to allow thesolution to push the blood out of the venous line 105 to the patient.Fluid balance control pump 303 continues to operate until a fluid volumesufficient to rinse the blood volume from venous line 105 back to thepatient has been pumped and then fluid balance control pump 303 isstopped. In any embodiment, the user can enter prompts through userinterface 801 to return additional increments of solution for furtherrinse back of venous line 105, or acknowledge that venous line 105 issufficiently rinsed back. When the user acknowledges that venous line105 is sufficiently rinsed back, venous pinch valve 401 closes toprevent further fluid ingress or egress through venous blood access line103.

In the next step, the user can disconnect the blood access 963, forexample by disconnecting patient blood access lines 103 and 104 fromconnection ports 501 and 502 of extracorporeal flow path 100 per thepatient's normal blood access procedures. Then, the user can verify therinse-back is complete 964. For example, in any embodiment the user cancommunicate via user interface 801 that patient's blood accessdisconnection has been completed.

FIG. 14 shows an evacuation procedure 906 in accordance with theinvention. For ease of shutdown and disposal, evacuation procedure 970can move fluid volume remaining in the system to a reservoir, forexample reservoir 201. The fluid volumes moved can include fluid volumefrom an extracorporeal flow path, consisting of solution that remains inthe extracorporeal circuit 100 after the blood has been rinsed back;fluid volume from an infusate reservoir, consisting of solution thatremains in an infusate reservoir at the end of a therapy session such asfluid remaining in reservoir 205; fluid volume removed from aconditioning conduit flow path, such as fluid remaining at the end of atherapy session in conditioning conduit flow path 115; fluid volumeremoved from a bypass conduit, such as fluid volume remaining in bypassflow path 111; and fluid volume removed from a solution flow conduit,including flow paths such as 110 or 120. The evacuation procedure can beinitiated 970, for example, by the user entering a request through theuser interface. First, the arterial line can be evacuated 971. Forexample, the system can remove the rinse back solution from arterialline 102 by opening arterial pinch valve 402 and operating blood pump302 and fluid control pump 303 toward solution reservoir 201 to move thesolution from arterial line 102 across dialysis membrane 702 tocontrolled compliant flow path 110 and into solution reservoir 201.Arterial pinch valve 402 can be closed and blood pump 302 stopped when asolution volume sufficient to drain arterial line 102 has been pumped.

Next, the venous line can be evacuated 972. For example, the system canremove the rinse back solution from venous line 105, dialyzer 701,microbial filter 706, and the portion of controlled compliant flow path110 from dialyzer inlet 506 to degassing module outlet 519 by openingvenous pinch valve 401, closing degassing vent valve 410, and operatingdialysate pump 305 in the reverse direction. Fluid balance control pump303 continues to remove fluid from controlled compliant flow path 110into solution reservoir 201 during this step. Pumping continues until avolume of fluid sufficient to drain this portion of the fluid circuithas been moved to solution reservoir 201 and then dialysate pump 305 isstopped. Control pump 303 continues to operate in the efflux directionand fluid in the portion of controlled compliant flow path 110 betweendialyzer outlet 507 and control pump 303 is moved to reservoir 201, andthen venous pinch valve 401 is closed and valve 407 is positioned tobypass flow path 111. With control pump 303 continuing to operate in theefflux direction, vent valve 410 is opened to drain the degassing module705 and that portion of the controlled compliant flow path 110 fromdegassing module outlet 519 to bypass valve 407. Pumping continues untila volume of fluid sufficient to drain this portion of the fluid circuithas been moved to solution reservoir 201.

Then, in the next step, electrolyte cartridges can be drained 973. Forexample, the sodium chloride cartridge 203, bicarbonate cartridge 204,and connecting lines can be drained to a void volume created within maincontrolled compliant flow path 110 by the preceding step. To accomplishthis, fluid balance control pump 303 is stopped, bypass valve 407 ispositioned or switched back to dialyzer inlet flow path, degassing ventvalve 410 is opened, venous pinch valve 401 is opened, and salinationpump 307 operates in reverse direction while the salination valve isdirected alternately between sodium chloride cartridge 203 flow path andbicarbonate cartridge 204 flow path. This action moves the fluid totemporary storage created in degassing module 705 and controlledcompliant flow path 110 by previous actions. When a volume of fluidsufficient to drain both cartridges and the conditioning flow path 115lines has been pumped to degas module 705 and main controlled compliantflow path 110, salination pump 307 is stopped.

In the next step, the bypass loop and degassing module can be evacuated974. For example, with reference to FIG. 1, the portion of controlledcompliant flow path 110 between degassing module 705 outlet 519 anddialyzer 701 can be drained by operating dialysate pump 305 in reversewith venous pinch valve 401 remaining open, vent valve 410 closed, andcontrol pump 303 operating in an efflux direction until a volumesufficient to drain the volume of fluid re-introduced to that portion ofcontrolled compliant flow path 110 by the preceding drainage of sodiumchloride cartridge 203 and bicarbonate cartridge 204 has been removed tocontrol reservoir 201. Then dialysate pump 305 is stopped, venous pinchvalve 401 is closed and bypass valve 407 is positioned or switched todirect flow through bypass flow path 111 and degassing vent valve 410 isopened with control pump 303 continuing to operate in the effluxdirection. Fluid balance control pump 303 operates to move fluid totherapy solution reservoir 201 until a volume of fluid sufficient todrain degassing module 705, the portion of the controlled compliant flowpath 110 from degassing module outlet 519 to valve 407, and priming andrecirculation bypass flow path 111 has been moved to solution reservoir201.

Then, the dialysate loop can be drained 975. For example, with referenceto FIG. 1, the remainder of controlled compliant flow path 110 can bedrained. Dialysate pump 305 can be operated in reverse with vent valve410 open and fluid balance control pump 303 operating in the effluxdirection to move fluid remaining in controlled compliant flow path 110between degassing module 705 inlet 516 and fluid balance control pump303 to solution reservoir 201. Finally, all pumps are stopped and thedegassing vent control valve 410 is closed. In any embodiment, the userinterface can display a message to the user that the evacuationprocedure is complete, and that therapy cassette 820 may be removed andreplaced with cleaning manifold 840. It will be recognized from thedetailed description of this invention that solution reservoir 201functions as a common reservoir of solution or fluid volume used formultiple purposes and originating from multiple sources or locationswithin the system. The reservoir may contain any one of a dialysate, afiltrate, a volume of a physiologically compatible priming solution, avolume of a physiologically compatible solution to provide a bolus offluid to a subject receiving treatment, a volume of physiologicallycompatible solution to provide solution for return of blood from anextracorporeal flow path to a subject receiving treatment, a volume ofsolution returned to the common reservoir from an extracorporeal flowpath when blood from a subject is introduced to the extracorporeal flowpath, and combinations thereof. Solution reservoir 201 further canreceive fluids that are drained from the extracorporeal flow path, thecontrolled compliant flow path, and/or an infusate reservoir followingconclusion of a treatment.

FIG. 15 shows a cleaning and disinfection procedure 907 in accordancewith the invention. The cleaning and disinfection procedure can beinitiated 981, for example, by the user acknowledging through userinterface the user's intent to remove the disposable and consumablecomponents, optionally grouped into a therapy cassette. In the nextstep, the user can remove the therapy cassette 982. For example, in anembodiment corresponding to FIGS. 1, 5G, 6A and 6B, arterial pinch valve402 and venous pinch valve 401 can be opened to allow arterial line 102and venous line 105 to be disengaged for cassette removal, and the usercan remove the therapy cassette. Then, the user can install a cleaningmanifold 983. For example, the user can remove the therapy cassette 820and install cleaning manifold 840 in place of therapy cassette 820 onthe system. In any embodiment, sensors can be activated to confirmcorrect loading of the cleaning manifold. In any embodiment, the systemmay optionally communicate through visual, audible, or tactile signalsto user during the process to confirm successful task completion, or toprovide corrective feedback.

In the next step, a water reservoir can be filled. For example, thesystem can display a message on the user interface 801 to prompt theuser to fill water reservoir 202 with sufficient water, includingpotable water, to execute the cleaning and disinfection cycle. It isnoted the system is not limited to potable water but can include othertypes of water prepared and/or treated by those of ordinary skill in theart suitable for use in the present dialysis systems and methodscontemplated by the present invention including peritoneal dialysis,hemodiafiltration and hemodialysis. The required amount of water canfurther be displayed on the user interface. In any embodiment, waterreservoir 202 can include a visual indicator of the minimum fill levelfor this process. The user can fill water reservoir 202 and reconnect itto cleaning manifold 820 connection ports 509BM and 510BM.Alternatively, in any embodiment, the user can transport water orpotable water to water reservoir 202 and fill it in place on the system.In some embodiments, sensors can be activated to confirm correct fillingand reconnection of the water reservoir.

In any embodiment, the system can intake and degas water from the waterreservoir 202 according to the same procedure as previously describedunder the de-aeration procedure described herein. With reference to FIG.3, the system can purify water from water reservoir 202 by passing thewater through the sorbent cartridge 703 while the pumps and valves aresequenced to flush clean water through each fluid circuit component tothe integral fluid reservoir contained in the cleaning manifold in orderto flush residual therapy solutions from controlled compliant flow path110, the conditioning flow path 115 through pump 307 and valve 406,bypass flow path 111, which can function in the present embodiment tobypass the dialyzer, and also metering pumps 303, 304, and 306 prior tofurther cleaning and/or disinfection.

In the next step, a cleaning and/or disinfection concentrate cartridgeis installed 985. For example, the user interface 801 can prompt theuser to remove sorbent cartridge 703 and connect the cleaning and/ordisinfection concentrate cartridge 720 into the controlled compliantflow path in place of sorbent cartridge 703 at connection ports 513 and514. The user can acknowledge through user interface 801 that thecleaning and/or disinfection concentrate cartridge 720 is installed. Inany embodiment, sensors can be activated to confirm correct connectionof the cleaning solution concentrate cartridge.

In the next step, a cleaning and/or disinfection sequence can beexecuted 986. For example, the user can enter a prompt through userinterface 801 to start an automated cleaning and/or disinfection cycle.After this action, the user may not be required to be present for theremainder of the process. The system can first circulate the watercontained in the controlled compliant flow path and jumper lumens of thecleaning reservoir in a recirculating loop through the cleaning and/ordisinfection solution concentrate cartridge by operating the pumps andvalves of controlled compliant flow path 110 to mix and distribute thecleaning and/or disinfection solution concentrate uniformly through allfluid pathways. The system heater 708 can heat the circulating cleaningand/or disinfection solution to a sufficient temperature to clean anddisinfect the fluid circuit while continuing to operate the pumps andvalves to circulate the cleaning and/or disinfection solution throughall fluid pathways until the disinfection process temperature isreached. The fluid temperature is monitored at control points to confirmthat the solution has reached the required disinfection temperaturethroughout the fluid circuit. The system continues to monitor andcontrol the fluid at the required disinfection temperature whileoperating the pumps and valves to circulate the heated cleaning and/ordisinfection solution through all fluid pathways until the required timeat temperature is completed. When the cleaning and/or disinfection cyclehas been completed, the heater and system pumps can be shut down.Optionally, the pumps can continue to run briefly following heatershutdown to allow residual heat to be safely dissipated from the heater.

In the next step, the hemodialysis system or device can be stored 987.For example, in an embodiment corresponding to FIG. 6B, the cleaningand/or disinfection solution can remain in the fluid circuit and thecleaning manifold 840 can be left in place on the system until thesystem is needed for the next therapy session. In any embodiment, thehemodialysis device can be folded into the storage and transportconfiguration with the fluid circuit filled with the cleaning and/ordisinfection solution and the cleaning manifold in place to ensure thatcontamination is not introduced to the fluid pathways prior to the nextuse.

The FIG.'s and specific examples provided herein illustrate a possibleembodiment of the invention and are non-limiting with respect to thespecific physical geometries of the various components depicted in theillustrations. It will be apparent to one skilled in the art thatvarious combinations and/or modifications can be made in the systems andmethods described herein depending upon the specific needs foroperation. Moreover, features illustrated or described as being part ofone embodiment may be used on another embodiment to yield a stillfurther embodiment.

We claim:
 1. A system for performing any one of hemodialysis,hemodiafiltration, hemofiltration, comprising: a controlled compliantflow path comprising a dialyzer; a single control pump in fluidcommunication with the controlled compliant flow path the control pumpfor selectively metering in and metering out fluid from the controlledcompliant flow path; and a common reservoir in fluid communication withthe control pump, wherein the control pump is a bidirectional pump,wherein the common reservoir contains any one of a dialysate, afiltrate, a volume of a physiologically compatible priming solution, avolume of a physiologically compatible solution to provide a bolus offluid to a subject receiving treatment, a volume of physiologicallycompatible solution to provide solution for return of blood from anextracorporeal flow path to a subject receiving treatment, a volume ofsolution returned to the common reservoir from an extracorporeal flowpath when blood from a subject is introduced to the extracorporeal flowpath, and combinations thereof.
 2. The system of claim 1, wherein thereservoir is in fluid communication with one or more conduits and asorbent cartridge, and wherein the dialysate is produced by the systemfor performing hemodialysis or hemodiafiltration from water introducedto a conduit of the controlled compliant flow path, the sorbentcartridge, a source of sodium introduced to a conduit of the controlledcompliant flow path, and optionally solutes other than sodium introducedto a conduit of the controlled compliant flow path.
 3. The system ofclaim 1, wherein the reservoir is in communication with one or moreconduits and a sorbent cartridge, and wherein the volume of aphysiologically compatible priming fluid is produced by the system fromwater introduced to a conduit of the controlled compliant flow path, thesorbent cartridge, a source of sodium introduced to a conduit of thecontrolled compliant flow path, and optionally solutes other than sodiumintroduced to a conduit of the controlled compliant flow path.
 4. Thesystem of claim 1, wherein the reservoir is in communication with one ormore conduits and a sorbent cartridge, and wherein the volume of aphysiologically compatible solution to provide a bolus of fluid to asubject receiving treatment is produced by the system from waterintroduced to a conduit of the controlled compliant flow path, thesorbent cartridge and a source of sodium introduced to a conduit of thecontrolled compliant flow path, and optionally solutes other than sodiumintroduced to a conduit of the controlled compliant flow path.
 5. Thesystem of claim 1, wherein the reservoir is in communication with one ormore conduits and a sorbent cartridge, and wherein the volume of aphysiologically compatible solution to provide fluid volume for returnof blood from the extracorporeal flow path to a subject receivingtreatment is the produced by the system from water introduced to aconduit of the controlled compliant flow path, sorbent cartridge, and asource of sodium introduced to a conduit of the controlled compliantflow path, and optionally solutes other than sodium introduced to aconduit of the controlled compliant flow path.
 6. The system of claim 2,3 or 5, wherein the reservoir is in communication with an extracorporealflow path, and wherein a portion of the fluid volume contained in thereservoir originates from a spent dialysate, a filtrate from the bloodof a subject, or a priming fluid that has been returned to thecontrolled compliant flow path from the extracorporeal flow path.
 7. Thesystem of claim 1, wherein the reservoir is in communication with one ormore conduits and a sorbent cartridge, and wherein the physiologicallycompatible priming fluid delivered from the common reservoir to aconduit of the controlled compliant flow path is in fluid communicationwith an extracorporeal flow path for priming of the extracorporeal flowpath wherein the priming fluid is passed through the sorbent cartridgeand at least a microbial filter or a dialyzer membrane.
 8. The system ofclaim 1, wherein the reservoir is in communication with anextracorporeal flow path, and wherein a volume of fluid is returned tothe common reservoir from an extracorporeal flow path when blood from asubject is introduced to the extracorporeal flow path.
 9. The system ofclaim 1, wherein the reservoir is in communication with one or moreconduits and a sorbent cartridge, and wherein the volume ofphysiologically compatible solution to provide solution for return ofblood from an extracorporeal flow path to a subject receiving treatmentis passed through the sorbent cartridge and is optionally infused by asource of cations introduced to a conduit of the controlled compliantflow path to produce the dialysate or a replacement fluid.
 10. Thesystem of claim 1, wherein the reservoir is in communication with asorbent cartridge and at least one of a microbial filter and dialyzermembrane, and wherein the volume of a physiologically compatiblesolution to provide a bolus of fluid to a subject receiving treatment isfirst passed through the sorbent cartridge and at least the microbialfilter or dialyzer membrane prior to being returned to theextracorporeal flow path.
 11. The system of claim 1, wherein thereservoir is in communication with a drain, and wherein the volume of aphysiologically compatible priming solution, the volume of aphysiologically compatible solution to provide a bolus of fluid to asubject receiving treatment, the volume of physiologically compatiblesolution to provide solution for return of blood from an extracorporealflow path to a subject receiving treatment, the volume of solutionreturned to the common reservoir from an extracorporeal flow path whenblood from a subject is introduced to the extracorporeal flow path, andcombinations thereof are drained from the common reservoir followingconclusion of a treatment.
 12. The system of claim 11, wherein thereservoir is in communication with one or more of an extracorporeal flowpath, or an infusate reservoir, and wherein volume of fluid in thereservoir further comprises fluids that are drained from theextracorporeal flow path, the controlled compliant flow path, or aninfusate reservoir following conclusion of a treatment.
 13. The systemof claim 1, further comprising a semi-permeable membrane, wherein theextracorporeal flow path is in fluid communication with the controlledcompliant flow path across the semi-permeable membrane wherein theextracorporeal flow path has a first terminal end and a second terminalend.
 14. The system of claim 13, wherein the first terminal end and thesecond terminal end are connectable together to form a junction.
 15. Thesystem of claim 14, wherein the junction is between the terminal ends ofan arterial line and a venous line of an extracorporeal circuit.
 16. Thesystem of claim 13, wherein the extracorporeal flow path has a bloodpump for circulating blood through the extracorporeal flow path, and afirst valve and/or a second valve to selectively permit flow through afirst conduit and a second conduit in fluid communication across eithera dialyzer or hemofilter on the extracorporeal flow path.
 17. The systemof claim 13, further comprising a first valve and/or a second valve,wherein at least the control pump coordinately operates with the firstvalve and/or a second valve to control fluid movement.
 18. The system ofclaim 14, further comprising a first valve and/or a second valve,wherein at least the blood pump coordinately operates with the firstand/or second valve to control fluid movement.
 19. The system of claim13, further comprising a first valve and/or a second valve, wherein thecontrol pump and a blood pump on the extracorporeal flow pathcoordinately operate with the first valve and/or second valve to controlfluid movement.
 20. The system of claim 14, wherein the extracorporealflow path has a hydrophobic vent or a priming overflow reservoirconnected to the junction.
 21. The system of claim 18 or 19, wherein atleast one of the first valve or second valve is a pinch valve.
 22. Thesystem of claim 13, further comprising a sorbent cartridge on thecontrolled compliant flow path wherein a fluid passes through thesorbent cartridge prior to crossing the semi-permeable membrane.
 23. Thesystem of claim 13, further comprising a microbial filter on thecontrolled compliant flow path wherein fluid passes through themicrobial filter prior to crossing the semi-permeable membrane.
 24. Thesystem of claim 13, further comprising a microbial filter on thecontrolled compliant flow path wherein fluid passes through themicrobial filter prior to entering the extracorporeal flow path.
 25. Thesystem of claim 13, further comprising at least one bubble detector todetect air in the extracorporeal flow path at any one of a firstconduit, a second conduit, or both.
 26. The system of claim 13, whereinthe controlled compliant flow path has a means for conductivitymeasurement to verify that a sodium content is within predeterminedlimits.
 27. The system of claim 13, wherein the controlled compliantflow path has a means for adjusting the solute concentration of fluid inthe controlled compliant flow path.
 28. The system of claim 27, whereinthe means for adjusting the solute concentration of fluid in thecontrolled compliant flow path is a sodium chloride source that canincrease a sodium chloride concentration of fluid passing through thecontrolled compliant flow path and a buffer source that can increase abuffer concentration of fluid passing through the controlled compliantflow path.
 29. The system of claim 27, wherein the means for adjustingthe solute concentration of fluid in the controlled compliant flow pathis a sodium chloride cartridge that can increase a sodium chlorideconcentration of fluid passing through the cartridge and a buffer sourcecartridge that can increase a buffer concentration of fluid passingthrough the buffer source cartridge.
 30. A method of priming a dialyzerand extracorporeal flow path using the system of claim 20, comprisingthe steps of: operating a control pump to transfer a first volume offluid from the control reservoir to a controlled compliant flow path;opening a second valve on the extracorporeal flow path while operatingthe control pump to transfer a second volume of fluid from the controlreservoir to the controlled compliant flow path; closing the secondvalve; opening an first valve on the extracorporeal flow path whilecoordinately operating the control pump and blood pump to transfer athird volume of fluid from the control reservoir to the controlledcompliant flow path and to the extracorporeal circuit; closing the firstvalve and stopping the control pump and the blood pump.
 31. The methodof claim 30, further comprising operation of a circulating pump in fluidcommunication with a controlled compliant flow path.
 32. The method ofclaim 30, wherein the first volume of fluid is approximately equal tothe priming volume of a dialyzer or a hemofilter; wherein opening thesecond valve causes an equal volume of fluid to move to theextracorporeal flow path, the second volume being approximately equal tothe priming volume of the second conduit of the extracorporeal flowpath; and the third volume being approximately equal to the primingvolume of the first conduit.
 33. The method of claim 30 furthercomprising the step of operating a circulating pump to move air from thedialyzer to a degassing module in fluid communication with thecontrolled compliant flow path.
 34. The method of claim 30, furthercomprising the steps of: opening the first and second valves andoperating the blood pump to circulate the priming fluid through theextracorporeal circuit; closing the first valve and stopping the bloodpump; operating the control pump to transfer a fourth volume of primingfluid to the controlled compliant flow path to cause an equal volume offluid to move through the second conduit to a priming overflow reservoirin fluid communication with the junction; closing the second conduit andoperating the control pump to transfer a fifth volume of fluid from thecontrol reservoir to the controlled compliant flow path while operatingthe blood pump in coordination with the control pump to cause an equalvolume of fluid to move through a first conduit to a priming overflowreservoir in fluid communication with the junction.
 35. A method ofinitiating a therapy session using the system of claim 13, comprisingthe steps of: connecting the first terminal end to a first blood accessconnection of a subject; opening a first valve on the extracorporealflow path while operating a blood pump; stopping the blood pump andclosing the second valve and disconnecting the second terminal end fromthe overflow reservoir, and connecting the second terminal end to asecond blood access connection of a subject.
 36. The method of claim 35,wherein opening the first valve moves a predetermined volume of bloodinto the extracorporeal flow path and displaces an approximately equalvolume of priming fluid to an overflow reservoir in fluid communicationwith the second terminal end.
 37. A method of returning a priming fluidand initiating a therapy session using the system of claim 13,comprising the steps of: connecting the second terminal end to a firstblood access connection of the subject; opening a second valve on theextracorporeal flow path while operating a control pump to move apredetermined first volume of blood into the extracorporeal flow path;stopping the control pump and closing the second valve and connectingthe first terminal end to a second blood access connection of thesubject; opening a first valve and operating a blood pump and thecontrol pump together at approximately equal volumetric flow rates tomove a second volume of blood into the extracorporeal flow path.
 38. Themethod of claim 37, further comprising displacing an approximately equalvolume of priming fluid from a first segment of the extracorporeal flowpath across the semipermeable membrane to a control reservoir on thecontrolled compliant flow path; and displacing an approximately equalvolume of priming fluid from a second segment of the extracorporeal flowpath across the semipermeable membrane to the control reservoir whereinthe first and second predetermined volumes are approximately equal tothe total priming volume of the extracorporeal flow path.
 39. A methodof returning a priming fluid and initiating a therapy session using thesystem of claim 13, comprising the steps of: connecting the firstterminal end to a first blood access connection of the subject; openinga first valve on the extracorporeal flow path while operating a controlpump to move a predetermined first volume of blood into theextracorporeal flow path; stopping the control pump and closing thefirst valve and connecting the second terminal end to a second bloodaccess connection of the subject; opening a second valve and operating ablood pump and the control pump together at approximately equalvolumetric flow rates to move a second volume of blood into theextracorporeal flow path.
 40. The method of claim 39, further comprisingdisplacing an approximately equal volume of priming fluid from a firstsegment of the extracorporeal flow path across the semipermeablemembrane to a control reservoir on the controlled compliant flow path;and displacing an approximately equal volume of priming fluid from asecond segment of the extracorporeal flow path across the semipermeablemembrane to the control reservoir, wherein the first and secondpredetermined volumes are approximately equal to the total primingvolume of the extracorporeal flow path.
 41. The method in any one ofclaims 30-38, wherein either the blood or control pump is abidirectional pump.
 42. A method for delivering a fluid bolus to asubject using the system of claim 13 or 22, comprising the steps of:transferring a predetermined volume of the physiological-compatiblefluid from the control reservoir to the controlled compliant flow pathto cause the physiological-compatible fluid to transverse a dialyzermembrane or a microbial filter from the controlled compliant flow pathto the extracorporeal flow path; and conveying the physiologicallycompatible fluid through the extracorporeal conduit flow path to thesubject.
 43. The method of claim 42, wherein the predetermined volume ofthe physiological-compatible fluid from the control reservoir is equalto the volume of the physiological-compatible fluid and wherein thevolume of the physiologically compatible fluid is equal to the volume inthe extracorporeal conduit flow path.
 44. The method of claim 42,further comprising measuring the conductivity of the fluid before itpasses to the extracorporeal flow path.
 45. The method of claim 42,further comprising operating an infusate pump to adjust a concentrationof a solute in the fluid before the fluid passes to the extracorporealflow path.
 46. A method for returning blood from an extracorporeal flowpath to a subject using the system of claim 13 or 22, comprising thesteps of: transferring a volume of fluid from the control reservoir tothe controlled compliant flow path to cause a volume of the fluid totransverse a dialyzer membrane or a microbial filter from the controlledcompliant flow path to the extracorporeal flow path; and conveying thevolume of the physiologically compatible fluid through theextracorporeal flow path to displace the blood from the extracorporealflow path to the subject.
 47. The method of claim 46, wherein the volumeof fluid from the control reservoir to the controlled compliant flowpath causes an equal volume of the fluid to transverse a dialyzermembrane or a microbial filter from the controlled compliant flow pathto the extracorporeal flow path and wherein the volume of thephysiologically compatible fluid is equal to the volume conveyed throughthe extracorporeal flow path to the subject.
 48. The method of claim 46,where the equal volume is approximately equal to a priming volume of theextracorporeal flow path.
 49. The method of claim 46, further comprisingthe steps of: conveying a first volume of the fluid through a firstsegment of the extracorporeal flow path; conveying a second volume ofthe fluid through a second segment of the extracorporeal flow path;wherein transferring the first volume of the fluid from the controlreservoir to the controlled compliant flow path causes a first equalvolume of the fluid to transverse the semipermeable membrane from thecontrolled compliant flow path to the extracorporeal flow path, andtransferring the second volume of the fluid from the control reservoirto the controlled compliant flow path causes a second equal volume ofthe fluid to transverse the semipermeable membrane from the controlledcompliant flow path to the extracorporeal flow path.
 50. The method ofclaim 49 wherein the first volume of the fluid approximately equals afirst priming volume of the first segment of the extracorporeal flowpath and the second volume of the fluid approximately equals a secondpriming volume of the second segment of the extracorporeal flow path.51. The method of claim 46, wherein a blood pump and a control pump areoperated coordinately to convey fluid through a conduit of theextracorporeal flow path.
 52. The method of claim 46, wherein thecontrol pump is a bidirectional pump.
 53. The method of claim 46,wherein the extracorporeal flow path has a blood pump for circulatingblood through the extracorporeal flow path, and a first valve and/or asecond valve to selectively permit flow through the tubing forming theextracorporeal flow path.
 54. The method of claim 46, wherein the meansfor selectively metering in and metering out fluid from the controlledcompliant flow path is a control pump in fluid communication with acontrol reservoir.
 55. The method of claim 46, wherein at least thecontrol pump coordinately operates with a first valve and/or a secondvalve to control fluid movement.
 56. The method of claim 46, wherein atleast the blood pump coordinately operates with the first valve and/orsecond valve to control fluid movement.
 57. The method of claim 46,wherein the control pump and a blood pump on the extracorporeal flowpath coordinately operate with the first valve and/or second valve tocontrol fluid movement.
 58. The method of claim 46, wherein at least oneof the first valve or second valve is a pinch valve.
 59. The method ofclaim 46, further comprising the step of passing a fluid through asorbent cartridge on the controlled compliant flow path wherein thefluid passes through the sorbent cartridge prior to crossing thesemi-permeable membrane into the extracorporeal flow path.
 60. Themethod of claim 46, further comprising the step of passing a fluidthough a microbial filter on the controlled compliant flow path whereinthe fluid passes through the microbial filter prior to crossing thesemi-permeable membrane into the extracorporeal flow path.
 61. Themethod of claim 46, wherein the controlled compliant flow path has ameans for conductivity measurement to verify that a sodium content iswithin predetermined limits.
 62. The method of claim 46, wherein thecontrolled compliant flow path has a means for adjusting theconductivity of fluid in the controlled compliant flow path.
 63. Thesystem of claim 13, wherein the semi-permeable membrane is in a formselected from the group of hollow fibers, flat sheets, and spiral wound.64. The system of claim 1, wherein the control pump is operable to pumpfluid bi-directionally to actively control the transfer of fluid volumeinto or out of a compartment or flow path.